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长期高饱和脂肪酸和高不饱和脂肪酸饮食诱导胰岛素抵抗大鼠肾动脉舒缩功能的变化

长期高饱和脂肪酸和高不饱和脂肪酸饮食诱导胰岛素抵抗大鼠肾动脉舒缩功能的变化
长期高饱和脂肪酸和高不饱和脂肪酸饮食诱导胰岛素抵抗大鼠肾动脉舒缩功能的变化

https://www.wendangku.net/doc/7817890910.html, Received 2006-12-29 Accepted 2007-02-13

This work was supported by the Natural Science Foundation of Hebei Province (No. 303552).

*Corresponding author. Tel: +86-311-85988340; Fax: +86-311-85988318; E-mail: sguangyao@https://www.wendangku.net/doc/7817890910.html,

Effects of long-term high-saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats

GAO Yu, SONG Guang-Yao *, MA Hui-Juan, ZHANG Wen-Jie, ZHOU Yu

Department of Geriatrics, Hebei Provincial People’s Hospital, Hebei Provinical Geriatric Key Laboratory, Shijiazhuang 050051,China

Abstract: The present study was designed to investigate the effects of high-saturated and high-unsaturated fatty acid diets on relaxation and contraction of the renal arteries in insulin resistance (IR) rats. Wistar rats were fed normal chow diet (control), high-saturated fatty acid diet or high-unsaturated fatty acid diet for 6 months (n =14 in each group). IR was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp. Blood pressure was measured via the tail-cuff method. Body weight (BW), plasma total trigly-ceride (TG), free fatty acid (FF A), insulin, fasting blood glucose (FBG) and nitric oxide metabolite (NO 2–/NO 3–) were compared among the three groups. The rats were sacrificed and the renal arterial rings were placed in the physiological tissue baths for measurement of vascular response to various agents. After the arterial rings were constricted with 3 mmol/L noradrenaline (NA), endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (NTP) were measured. Endothelium-dependent vasorelaxation to ACh was also observed in renal arterial rings incubated with L -arginine (L -Arg),N ω-nitro-L -arginine (L -NNA) and methylene blue (MB), respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 μmol/L NA. Saturated or unsaturated fatty acids led to moderate rises in blood pressure (P <0.05).It was associated with higher levels of plasma lipids and lower whole body insulin sensitivity (P <0.01). There were no significant differences in BW, FBG, TG, insulin and FFA between saturated and unsaturated fatty acid-fed rats. A decrease in endothelium-dependent vasorelaxation of the renal arteries in saturated and unsaturated fatty acid-fed rats was observed (P <0.01), but there was no marked difference between the two high-fatty acid diet groups. Endothelium-dependent vasorelaxation was increased when the arteries were incubated with L -Arg and decreased when incubated with L -NNA and MB in both high-fatty acid diet groups (P <0.05, P <0.01).But no difference was found before and after incubation with L -Arg, L -NNA and MB in the control rats. In the mean time, endothelium-independent maximal vasorelaxation response of renal arteries to NTP and renal arterial contractile responses to cumulative dose of NA were assayed, and there was no difference among the three groups (P >0.05). Endothelium-dependent vasorelaxation was negatively correlated with systolic blood pressure and TG, and positively correlated with NO 2–/NO 3– and GIR. There was a significantly negative correlation between FFA and NO 2–/NO 3–. The present study suggests that both high-saturated and unsaturated fatty acid diets result in hypertension associated with significantly decreased endothelium-dependent vasorelaxation, dyslipidemia and IR, and that de-creased endothelium-dependent vasorelaxation induced by high fatty acid diets is associated with impaired L -Arg-NO-cGMP pathways.Key words: endothelium; vasorelaxation; vasoconstriction; nitric oxide; diet; hypertension; insulin resistance

长期高饱和、高不饱和脂肪酸饮食诱导胰岛素抵抗大鼠肾动脉舒张和收缩功能的变化

高 宇,宋光耀*,马慧娟,张文杰,周 宇

河北省人民医院老人病科,河北省老年医学重点实验室,石家庄 050051

摘 要:本文旨在探讨长期高饱和、高不饱和脂肪酸饮食诱导胰岛素抵抗(insulin resistance, IR)大鼠肾动脉舒张和收缩功能的变化。成年Wistar 大鼠随机分为对照组、高饱和脂肪酸组和高不饱和脂肪酸组,每组14只。喂养6个月后,用高胰岛素正常葡萄糖钳夹技术的葡萄糖输注率(glucose infusion rate, GIR)评价IR ;用尾套法测定大鼠血压,同时比较三组大鼠的体重、 Research Paper

血清甘油三酯、游离脂肪酸、胰岛素、空腹血糖和NO代谢产物NO

2_

/NO

3

_

。大鼠处死后,取肾动脉放入生理盐溶液中,

观察血管对各种因子的舒、缩反应。结果显示,喂养6个月后,与对照组大鼠比较,高饱和脂肪酸组和高不饱和脂肪酸组大鼠均出现血压升高、血清甘油三酯升高和胰岛素敏感性降低;体重、空腹血糖、胰岛素和游离脂肪酸均升高(P<0.01);而两高脂组间体重、空腹血糖、胰岛素和游离脂肪酸无显著性差异。高饱和脂肪酸组大鼠肾动脉对ACh的内皮依赖性最大舒张反应(R

max

)最低,其次为高不饱和脂肪酸组和对照组;对照组与两高脂组有显著性差异(P<0.01),而两高脂组间无显著

性差异。血管经L-Arg孵育后,两高脂组肾动脉对ACh的内皮依赖性R

max

均比孵育前增加,经Nω-硝基-L-精氨酸(Nω-nitro-

L-arginine, L-NNA)及美蓝(methylene blue, MB)孵育后,两高脂组R

max

均比孵育前降低(P<0.05, P<0.01); 对照组各孵育液之间无

显著性差异(P>0.05)。肾动脉对硝普钠的非内皮依赖性R

max

及对去甲肾上腺素的收缩反应,三组间无显著性差异(P>0.05)。相

关分析结果显示,肾动脉对ACh的内皮依赖性R

max 与收缩压、甘油三酯呈明显负相关,与NO

2

_

/NO

3

_

和GIR呈明显正相

关,游离脂肪酸与NO

2_

/NO

3

_

呈明显负相关。结果提示,高饱和及高不饱和脂肪酸饮食均可引起高血压及与之密切相关的

内皮依赖性血管舒张功能减弱、高脂血症和IR,高脂诱导内皮依赖性血管舒张功能减弱与L-Arg-NO-cGMP通路受损有关。

关键词:内皮;血管舒张;血管收缩;一氧化氮;饮食;高血压;胰岛素抵抗

中图分类号:R587

A group of syndromes including hyperglycemia, hypertension, hyperlipidemia and obesity have been termed as “metabolic syndrome”, because of the extremely high atherogenic profile it creats. It has been suggested that impaired vasorelaxation may lead to hypertension, while endothelial vasomotor dysfunction may predict long-term atherosclerotic disease progression and the rate of cardio-vascular events[1,2].

The vascular endothelium plays a significant regulatory role in many physiological processes in the body, includ-ing the regulation of vasomotor tone via a range of bioactive substances. Nitric oxide (NO) and endothelin-1 (ET-1) are two important factors derived from the endothelium and they exert opposite influences on vascular tone[3]. Previous work in our laboratory has shown that synthesis of NO and ET-1 was inhibited in human umbilical vein endothelial cells (HUVECs) incubated with different kinds of free fatty acids (FFAs). In the present study, to explore the possible mechanism of vascular complication in metabolic syndrome, male Wistar rats fed with high-saturated and unsaturated fatty acid diets were used to observe the influence of different diets on relaxation and contraction of renal arteries, and the in relation with altered lipidemia and insulin sensitivity .

1 MATERIALS AND METHODS

1.1 Animals

Male Wistar rats supplied by the Experimental Animal Cen-ter of Hebei Medical University were conditioned at (22±0.5) o C in 12-hour light/12-hour dark cycle for one week in communal cages. Animals were fed ad libitum a standard chow diet for at least a week before experimental diets.After habituation, rats (250-300 g) were randomized to three matched groups (n=14 in each group). (1) Control group: continued to be fed ad libitum a low fatty acid diet, containing 10% fat, 24% protein and 66% carbohydrate as percentage of total calories. (2) High-saturated fatty acid diet (HSF) group: fed regular diets mixed with 20% butter, containing 41% fat (total saturated fatty acid 28% and un-saturated fatty acid 13% mainly containing palmitic acid), 16% protein and 43% carbohydrate as percentage of total calories. (3) High-unsaturated fatty acid diet (HUF) group: fed regular diets mixed with 20% soybean oil, containing 41% fat (total saturated fatty acid 6.6% and unsaturated fatty acid 34.4% mainly containing oleate), 16% protein and 43% carbohydrate as percentage of total calories. The soybean oil and butter were obtained from the Experimen-tal Animal Center of Hebei Medical University. The sys-tolic blood pressure was recorded by using the tail-cuff plethysmographic method under conscious conditions.

1.2 Hyperinsulinemic euglycemic clamp Experiment was conducted between 9:00 and 12:00 in 12-hour fasted animals after 6 months. After being weighed, rats were anesthetized with pentobarbitone (40 mg/kg, i.p.). The left femoral vein was exposed and a catheter was inserted for infusion of glucose and insulin. Another catheter was inserted into the femoral artery for blood sampling. A 30-minute basal period was followed to reach steady state. Then a 120-minute hyperinsulinemic eugly-cemic clamp was performed according to Kraegen et al[5]. In brief, human insulin (Actrapid, Novo-Nordisk, China) was infused at a constant rate of 1.67 mU/kg per minute and the arterial blood glucose concentration was clamped at the basal fasting level by infusing glucose at variable rates. Under the hyperinsulinemic conditions, the steady

GAO Yu et al : High-Saturated and Unsaturated Fatty Acid Diets on Relaxation and Contraction of Renal Arteries in IR Rats

365

glucose infusion rate (GIR) required to maintain euglycemia (usually calculated between 60-120 min) is a standard measure of the whole-body insulin sensitivity.1.3 Analytical methods

Blood glucose levels were measured with a quick glucose analyzer (Roche, Germany). Plasma immunoreactive in-sulin concentration was assayed by radioimmunoassay.Plasma triglyceride was determined on an automatic bio-chemistry analyzer (Beckman X20, America). Serum-FFA and NO 2–/NO 3– were determined using copper coloration and nitrate reductase kits, respectively (Jiancheng Biologi-cal Corporation, Nanjing).

1.4 Assessment of vascular function

Four third-order renal arteries (300-500 μm diameter, 1.5mm) were carefully dissected from each animal. Each ar-tery was free of fat and connective tissue and mounted on two 40-μm diameter steel wires through the lumen on an automated Mulvany myograph (Model 610M, J.P. Trad-ing I/S, Denmark). One wire was fixed to a displacement micrometer and the other was connected to a tension transducer. Four arteries at a time were incubated in 5 mL organ bath containing physiological salt solution (PSS) (in mmol/L): NaCl 119, KCl 4.7, CaCl 2 2.5, MgSO 4·7H 2O 1.17, NaHCO 3 25, KH 2PO 4 1.18, EDTA 0.027, glucose 5.5), gassed with 95% O 2 and 5% CO 2 at 37 o C.

After an equilibration period of 30 min, the tissue was normalized to 90% of the inner circumference that corres-ponds to 100 mmHg blood pressure [6], using a non-linear curve-fitting programme developed by McPherson et al [7].The setting represents a resting tension of 2-3 mN under the present experimental condition. The arteries were al-lowed a further 30 min to equilibrate before being depola-rized twice with high-potassium PSS (KPSS), in which NaCl in the normal PSS was replaced by an equimolar concentration of KCl (final [K +]=125 mmol/L). Any artery failing to reach its predetermined target tension in response to KPSS was discarded.

Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 μmol/L noradrenaline

(NA). Arterial relaxation was measured in NA-precontracted arteries following exposure to endothelium-dependent vasorelaxant acetylcholine (ACh), and endothelium-independent vasodilator sodium nitroprusside (NTP). Arterial ring segments were contracted with 3 mmol/L NA. When contraction reached a plateau (after 2 min), concentration-response curves to ACh and NTP over the range of 10nmol/L-100 μmol/L were carried out. Arterial ring segments were incubated with L -arginine (L -Arg, substrate of nitric oxide synthase), N ω-nitro-L -arginine (L -NNA, inhibitor of nitric oxide synthase ) and methylene blue (MB, inhibitor of guanylate cyclase), respectively, for 20 min, then the arterial relaxation response to ACh was recorded. During each experiment, PSS was changed every 15-20 min.1.5 Statistics

Contractile responses to NA were expressed as absolute tension generated and the tension of vessel was measured in mN/mm, while relaxation response to each concentra-tion of ACh and NTP was calculated as the percentage of reduction from the maximal tension induced by 3 mmol/L NA. All data were expressed as means±SEM. Analyses of variance (ANOV A) were used to assess the changes from the baseline and the differences among groups when appropriate. Student’s t -test was used to evaluate data be-tween two comparisons. P <0.05 was considered statisti-cally significant.

2 RESUL TS

2.1 Metabolic data

Body weight, fasting blood glucose, plasma triglyceride,insulin and FFA in HSF and HUF groups were significantly higher than that in the control group, whereas the levels of NO 2–/ NO 3– were significantly lower than that in the con-trol group (P <0.01). There was no difference in the above-mentioned parameters between HSF and HUF groups ex-cept that the level of NO 2–/ NO 3– in HSF group was lower than that in HUF group (P <0.05)(Table 1).2.2 Systolic blood pressure

Table 1. Comparison of metabolic parameters in Wistar rats 6 months after feeding different diets

Group

BW FBG TG INS NO 2–/NO 3– FFA (g)

(mmol/L)

(mmol/L) (mU/L) (μmol/L) (mmol/L)

Normal chow diet

450.00±60.39 5.26±0.340.95±0.1920.81±1.7964.79±15.460.78±0.07High-saturated fatty acid diet 507.86±49.32△ 6.76±0.45△ 1.69±0.17△38.75±6.83△17.40±7.29△ 1.33±0.35△High-unsaturated fatty acid diet

506.42±36.59△

6.62±0.66△

1.27±0.04△

37.75±8.57△

31.52±5.93*△

1.22±0.40△

BW, body weight; FBG, fasting blood glucose; TG, plasma triglyceride; INS, serum insulin; FFA, free fatty acid. means±SEM, n =8.△

P <0.01 vs normal chow diet group, *P <0.05 vs high-saturated fatty acid diet group.

Acta Physiologica Sinica, June 25, 2007, 59 (3): 363-368 366

The systolic blood pressure in HSF group [mean (131.57±6.40) mmHg] and in HUF group [mean (128.00±4.65) mmHg] was significantly elevated compared with that in the control group [mean (100.83±18.00) mmHg] (P<0.01).

2.3 Assessment of insulin resistance (IR)

The whole-body insulin sensitivity was assessed by GIR. GIR in HSF and HUF groups was (5.75±0.84) and (5.95±1.50) mg/kg per minute, respectively, significantly lower than that in the control group [(9.25±0.84) mg/kg per minute], clearly indicating the presence of IR. There was no significant difference in the degree of IR between HSF and HUF groups.

2.4 Contractile responses of renal arteries

There was no significant difference in the maximal con-traction to NA among the three groups [control group: (1.20±0.27) mN/mm;HSF group: (1.04±0.21) mN/mm; HUF group: (1.17±0.23) mN/mm]. There was no diffe-rence in the renal arterial contractility to NA (10 nmol/L-100μmol/L), either (Fig.1).

2.5 Endothelium-independent relaxation

Renal arterial ring segments were tested for endothelium-independent relaxation response to NTP. In all groups the arteries relaxed in response to NTP in a dose-dependent manner. At the maximal concentration of NTP (100 μmol/ L), the renal arterial ring in HSF group relaxed to (88.3±6.4)%, that in HUF group relaxed to (86.8±4.7)%, and that in the control group relaxed to (92.2±10.1)%. Despite blunted vasorelaxation at lower dose (i.e., 1×10–8-1×10–6 mol/L), the maximal NTP-induced relaxation remained un-changed in both HSF and HUF groups compared with that in the control group (Fig.2).

2.6 Endothelium-dependent relaxation

As shown in Fig.3, in both HSF and HUF groups, the sus-tained vasorelaxation was substantially impaired at all con-centrations of ACh tested (P<0.01). The maximal relaxa-tion induced by ACh was (43.1±1.8)% and (47.8±2.1)% in HSF and HUF groups, respectively, approximately half of that in the control group (80.5±8.1)%. However there was no statistic difference in the relaxation between HSF and HUF groups. Endothelium-dependent maximal relaxation to ACh was increased significantly by L-Arg in HSF group

Fig.1. Vasocontraction of isolated renal arteries to increasing doses of noradrenaline. Control, normal chow diet; HSF, high-saturated fatty acid diet; HUF, high-unsaturated fatty acid diet. means±SEM, n=6.Fig.2. Vasorelaxation of preconstricted isolated renal arteries to sodium nitroprusside. Control, normal chow diet; HSF, high-saturated fatty acid diet; HUF, high-unsaturated fatty acid diet. means±SEM, n=6. #P<0.01 vs control.

Fig.3. Vasorelaxation of preconstricted isolated renal arteries to acetylcholine. Control, normal chow diet; HSF, high-saturated fatty acid diet; HUF, high-unsaturated fatty acid diet. means±SEM. #P<0.01 vs control.

GAO Yu et al : High-Saturated and Unsaturated Fatty Acid Diets on Relaxation and Contraction of Renal Arteries in IR Rats

367

[(64.7±5.0)%] and in HUF group [(59.7±7.1)%] (P <0.05). L -NNA and MB reduced the maximal relaxation in-duced by ACh in HSF and HUF groups (P <0.01, P <0.05)(Fig.4).

2.7 Correlation analysis

We examined the relationships between endothelium-dependent vasorelaxation and systolic blood pressure,plasma triglyceride, NO 2–/ NO 3–, GIR. There was a nega-tive correlation between plasma triglyceride (r = –0.4570,P =0.0166) and systolic blood pressure (r = –0.4076, P =0.0348) and ACh-induced maximal vasorelaxation. There was a significant positive correlation between NO 2–/ NO 3–(r = 0.4353, P =0.028) and systolic blood pressure (r =0.4079, P =0.0347) and ACh-induced vasorelaxation. There was significant negative correlation between FFA and NO 2–/NO 3– (r = –0.4085, P =0.0344).

3 DISCUSSION

Not only epidemiologic survey but also empirical study suggests that IR is associated with obesity or excessive energy intake. In the present experiment, the effects of saturated and unsaturated fatty acids-enriched diet on de-veloped hypertension, hypertriglyceridemia, hype-rinsulinemia, obesity and induced IR were studied. It has been suggested that unsaturated fatty acids provided 30%calories bene-fited glucose and lipid metabolism [8]. But it was found that long-term diet rich in high-unsaturated fatty

acids brought the same risks as that rich in high-saturated fatty acids in our study.

Normal endothelial function is important in the control of vascular tone and subsequent regulation of blood pres-sure and blood flow to organs and tissues. The present study investigated the effect of diet rich in saturated and unsaturated fatty acids on vascular tension and the relation with impaired endothelium-dependent vasorelaxation but normal vascular contractile function. While still largely re-sponding to NTP, the isolated renal arteries from these high fatty acids-fed rats were not sensitive to ACh, indi-cating a link of impaired endothelial vasodilation of the ar-teries and the elevated systemic blood pressure.

As one of the chief endothelium-derived relaxant factors,NO is important in regularizing vascular tone. NO is a kind of unstable gas and it can easily diffuse through the cell membrane to dilate vascular smooth muscle. NO is syn-thesized from L -Arg and oxygen by nitric oxide synthase.The endothelial nitric oxide synthase plays a pivotal role in controlling NO synthesis [9]. NO is released from endothe-lial cells and diffuses to vascular smooth muscle binding guanylate cyclase on cell membrane and stimulates cGMP which exerts relaxation in vascular smooth muscle [10]. Our results showed that inhibition of nitric oxide synthase with L -NNA or inhibition of guanylate cyclase with MB reduced ACh-induced relaxation and substrate of nitric oxide syn-thase L -Arg increased ACh-induced relaxation significantly in HSF and HUF groups. This suggests endothelium-derived NO is involved in impaired endothelial function and the dysfunction may be associated with impaired L -Arg-NO-cGMP pathways by saturated or unsaturated fatty acid diets. Stulak et al .[10] found the similar results from aorta endothelium in rats fed high-cholesterol diets. Further studies are required to elucidate the detailed mechanism.

The cellular mechanisms behind endothelial dysfunction due to high-fat diets remain undefined. In the present research, rats fed saturated and unsaturated fatty acid diets increased plasma triglyceride levels. Some researches showed that the elevated triglyceride is also associated with decreased endothelium-dependent vasorelaxation [11]. Endo-thelial dysfunction related to hyperlipidemia and athero-sclerosis has been postulated to be the result of increased oxidant stress, leading to superoxide and oxygen free radi-cal production, and free radicals may then inactive NO upon contact [12]. It may be a mechanism for the decreased endothelial responsiveness shown in HSF and HUF groups.In recent studies, FFA elevation is regarded to play an important role in endothelial dysfunction [13]. FFA elevation may cause vascular endothelial dysfunction either indirectly

Fig.4. Acetylcholine-induced maximal relaxation of preconstricted isolated renal arteries from rats fed normal chow diet (control),high-saturated fatty acid diet (HSF) and high-unsaturated fatty acid diet (HUF). Acetylcholine was added in the presence of 1×10–3 mol/L L -arginine (L -Arg), 1×10–4 mol/L N ω-nitro-L -arginine (L -NNA) or 1×10–5 mol/L methylene blue (MB).means±SEM. #P <0.01, *P <0.05 vs control.

Acta Physiologica Sinica , June 25, 2007, 59 (3): 363-368368via increased release of vasoconstrictor substances such as ET-1 and/or through a direct impairment of basal NO production. Davda et al .[14] and Gupta et al .[15] demon-strated that in endothelial cell cultures FFA elevation inhibits NO production by decreasing endothelial nitric oxide synthase activity because endothelial nitric oxide synthase protein content was not altered by FFA elevation. Our re-search found plasma FFA increased and NO 2–/ NO 3– de-creased in the rats fed high saturated and unsaturated fatty acids. With a significant correlation between NO 2–/ NO 3–,GIR and FFA in HSF and HUF groups, we assume that the results may be attributable to decreased endothelium-dependent vasorelaxation and IR.

In summary, we have shown that rats fed two different high fat diets rich in saturated and unsaturated fatty acids develop obesity, hypertension, hypertriglyceridemia,hyperinsulinemia, and there is no difference between them in the present study. It appears to be a direct correlation between high-fatty acid diets and the development of en-dothelial dysfunction (reduction of endothelium-dependent vasorelaxation response to ACh), and may lead to the vas-cular complication in patients with type 2 diabetes mellitus.

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barrier dysfunction without disrupting the arginine-nitric oxide pathway. Am J Physiol 1998; 274: L508-L516.

饱和脂肪酸与不饱和脂肪酸

饱和脂肪酸与不饱和脂肪酸 根据其结构不同可分为三大类:饱和脂肪酸、单不饱和脂肪酸和多不饱和脂肪酸, 单不饱和脂肪酸和多不饱和脂肪酸统称不饱和脂肪酸。 (一)饱和脂肪酸 饱和脂肪酸的主要来源是家畜肉和乳类的脂肪,还有热带植物油(如棕榈油、椰子油等),其主要作用是为人体提供能量。它可以增加人体内的胆固醇和中性脂肪;但如果饱和脂肪摄入不足,会使人的血管变脆,易引发脑出血、贫血、易患肺结核和神经障碍等疾病。 (二)单不饱和脂肪酸 单不饱和脂肪酸主要是油酸,含单不饱和脂肪酸较多的油品为:橄榄油、芥花籽油、花生油等。它具有降低坏的胆固醇(LDL),提高好的胆固醇(HDL)比例的功效,所以,单不饱和脂肪酸具有预防动脉硬化的作用。 (三)多不饱和脂肪酸 多不饱和脂肪酸虽然有降低胆固醇的效果,但它不管胆固醇好坏都一起降,且稳定性差,不适合加热,在加热过程中容易氧化形成自由基,加速细胞老化及癌症的产生。多不饱和脂肪酸主要是亚油酸、亚麻酸、花生四烯酸等;其中亚油酸、亚麻酸为必需脂肪酸。含多不饱和脂肪酸较多的油有:玉米油、黄豆油、葵花油等 对健康区别 不饱和脂肪酸主要包括单不饱和脂肪酸和多不饱和脂肪酸,它们分别都对人体健康有很大益处。人体所需的必需脂肪酸,就是多不饱和脂肪酸,可以合成DHA(二十二碳六烯酸)、EPA(二十碳五烯酸)、AA(花生四烯酸),它们在体内具有降血脂、改善血液循环、抑制血小板凝集、阻抑动脉粥样硬化斑块和血栓形成等功效,对心脑血管病有良好的防治效果等等。DHA亦可提高儿童的学习技能,增强记忆。单不饱和脂肪酸可以降低血胆固醇、甘油三酯和低密度脂蛋白胆固醇(LDL-C)的作用。虽然不饱和脂肪酸虽然益处很多,但易产生脂质过氧化反应,因而产生自由基和活性氧等物质,对细胞和组织可造成一定的损伤。 饱和脂肪酸摄入量过高是导致血胆固醇、甘油三脂、LDL-C升高的主要原因,继发引起动脉管腔狭窄,形成动脉粥样硬化,增加患心脑血管疾病的风险。 稳定性区别 饱和脂肪酸由于没有不饱和键,所以很稳定,不容易被氧化;不饱和脂肪酸,尤其是多不饱和脂肪酸由于不饱和键增多,所以不稳定,容易被脂质过氧化反应。不适合加热,在加热的过程中容易氧化形成自由基,加速细胞的老化和癌症的产生。) 不饱和脂肪酸的生理功能 1.保证细胞的正常生理功能。 2.降低血液中胆固醇和甘油三酯。 3.是合成人体内前列腺素所必需。 4.降低血液粘稠度,改善血液微循环。 5.提高脑细胞的活性,增强记忆力和思维能力

不饱和脂肪酸

不饱和脂肪酸 缺乏脂肪,和缺乏其它任何一种营养一样,都会造成身体的不适。脂肪经消化后,分解成甘油及各种脂肪酸。 根据结构不同,脂肪酸分为饱和脂肪酸和不饱和脂肪酸,其中不饱和脂肪酸根据双健个数的不同,分为单不饱和脂肪酸和多不饱和脂肪酸(PUSA)两种。单不饱和脂肪酸有油酸,多不饱和脂肪酸按照从甲基端开始第1个双键的位置及功能不同,又分为ω-6系列和ω-3系列。亚油酸和花生四烯酸属ω-6系列,亚麻酸、DAH、EPA属ω-3系列,ω-3同维生素、矿物质一样是人体的必需品,不足容易导致心脏和大脑等重要器官障碍。人体不能合成亚油酸和亚麻酸,必须从膳食中补充。 ω-3不饱和脂肪酸中对人体最重要的两种不饱和脂肪酸是DHA和EPA。EPA是二十碳五烯酸的英文缩写,具有清理血管中的垃圾(胆固醇和甘油三酯)的功能,俗称"血管清道夫"。DHA是二十二碳六烯酸的英文缩写,具有软化血管、健脑益智、改善视力的功效,俗称"脑黄金"。 ω-3 多不饱和脂肪酸,是由寒冷地区的水生浮游植物合成,以食此类植物为生的深海鱼类(野鳕鱼、鲱鱼、鲑鱼等)的内脏中富含该类脂肪酸。1970年,两位丹麦的医学家霍巴哥和洁地伯哥经过研究确信:格陵兰岛上的居民患有心脑血管疾病的人要比丹麦本土上的居民少得多。格陵兰岛位于北冰洋,岛上居住的爱斯基摩人以捕鱼为主,他们喜欢吃鱼类食品。由于天气寒冷,他们极难吃到新鲜的蔬菜和水果。就医学常识来说,常吃动物脂肪而少食蔬菜和水果易患心脑血管疾病,寿命会缩短。但是事实恰恰相反,爱斯基摩人不但身体健康,而且在他们之中很难发现高血压、冠心病、脑中风、脑血栓、风湿性关节炎等疾病。无独有偶,这种不可思议的现象同样也发生在日本的北海道岛上。当地渔民的心脑血管疾病发病率明显低于其它区域,北海道人心脑血管疾病发病率只有欧美发达国家的1/10。在我国,也有研究发现浙江舟山地区渔民血压水平较低。其实问题就在于上述这些人的膳食中以鱼类为主,鱼类富含长链的不饱和脂肪酸,这就是他们保持心血管健康的原因之一。 但是日常生活中大多数人不能像爱斯基摩人那样天天吃深海鱼,同时由于生产和加工方面的技术原因,使人对一些食品中含有的不饱和脂肪酸吸收利用率很低,因此导致体内多不饱和脂肪酸严重缺乏,而饱和脂肪酸却大量积累。 主要功效 一、不饱和脂肪酸的生理功能 1、保持细胞膜的相对流动性,以保正细胞的正常生理功能。 2、使胆固醇细化,降低血中胆固醇和甘油三酯。 3、是合成人体内前列腺素和凝血恶烷的前躯物质。 4、降低血液粘稠度,该善血液微循环。 5、提高脑细胞的活性,增强记忆力和思维能力。 二、膳食中不饱和脂肪酸盈缺和健康 1、血中低密度脂蛋白和低密度胆固醇增加,产生动脉粥样硬化,诱发心脑血管病。 2、ω-3不饱和脂肪酸是大脑和脑神经的重要营养成份,摄入不足将影响记忆力和思维力,对婴幼儿将影响智力发育,对老年人将产生老年痴呆症。 膳食中过多时,干扰人体对生长因子、细胞质、脂蛋白的合成,特别是ω-6系列不饱和脂肪酸过多将干扰人体对ω-3不饱和脂肪酸的利用,易诱发肿瘤。 三、推荐的日摄入量 多不饱和脂肪酸含量是评价食用油营养水平的重要依据。豆油、玉米油、葵花籽油中,ω-6系列不饱和脂肪酸较高,而亚麻油、苏紫油中ω-3不饱和脂肪酸含量较高。由于不饱和脂肪酸极易氧化,食用它们时应适量增加维生素E的摄入量。一般ω-6:ω-3应在4 -10:1,摄入量为摄入脂肪总量的50% -60% 。 四、食物来源 1、脂肪的热量密度(1克= 9卡路里)是碳水化合物或蛋白质(1克=4卡路里)的两倍。尽管橄榄油和菜籽油对健康有益,但它们的热量也很高(1汤匙=120卡路里)。此外,许多加工食品和快餐食品的脂肪含量也较高,尤其是饱和脂肪。 2、多不饱和脂肪存在于红花籽油、印加果油、茶油、橄榄油、阿甘油、芥花籽油、葵花籽油、玉米油和大豆油中。而饱和脂肪存在于畜产品中,例如黄油、干酪、全脂奶、冰淇淋、奶油和肥肉,以及某些植物油(椰油、棕榈油和棕榈仁油)中。经科学家最新研究发现:来自南美洲亚马逊流域天然无污染的肥沃土壤中的印加果堪称世界植物营养“果王”,由此,印加果荣获巴黎世界博览会金奖。印加果油是目前世界上发现唯一含α-亚麻酸ω- 3、ω-6、ω-9三种不饱和脂肪酸高达92%的纯天然植物,独一无二,高含量亚麻酸被誉为“21世纪人类健康的加油站”,是不可忽视的生命活力素和消除亚健康的理想产品。 五、含其的植物油 可滋泉巴马火麻油是大自然中唯一能溶解于水的油料,在所有植物油中不饱和脂肪酸含量最高,同时含有大量延缓衰老的维生素E、硒、锌、锰、锗,还含有被誉为“植物脑黄金”的α-亚麻酸(ALA)。巴马火麻对自然生长环境要求极为苛刻,目前只产于巴马北部的石山,产量稀少且价格昂贵。 巴马火麻是迄今为止发现最有效的抗衰老和抗辐射植物,当地称之为“长寿麻”或“不老油”。鉴于在美容养颜和抗衰老方面的潜在价值,1999年联合国粮油调查署考察巴马火麻后向全世界特别推荐巴马火麻油为“最有开发价值的植物油”。 沙棘籽油也是典型的不饱和酸植物油,在所有植物油中不饱酸种类及含量都相当高,同时富含天然稳定剂维生素E,天

n-3多不饱和脂肪酸与恶性肿瘤

中华普通外科学文献 渊电子版冤 圆园员员 年 员圆 月第 缘 卷第 远 期 悦 澡蚤 灶 粤 则 糟 澡 郧 藻 灶 杂怎则 早渊耘 造 藻 糟 贼 则 燥 灶蚤 糟耘 凿蚤 贼 蚤 燥 灶冤袁 阅 藻 糟 藻 皂 遭藻 则圆园员员袁 灾 燥 造 缘 晕 燥 援 远 窑讲座与综述窑 DOI:10.3877/cma.j.issn.1674-0793.2011.06.016 作者单位:510080 广州,中山大学附属第一医院东山院区外科 n-3 多不饱和脂肪酸主要来源于多脂的深海冷水鱼,人类很难完整地合成 n-3 多不饱和脂肪酸,主要 通过食物摄取遥流行病学调查显示,增加 n-3 多不饱和脂肪酸摄取量可以抑制多种肿瘤的发生尧发展,减轻 进展期恶性肿瘤患者恶病质症状, 减少体重丢失甚至增加体重遥 但近年来也有学者对这一观点提出了异 议遥 人类约有 2/3 以上疾病的发生与膳食不当有关遥 越来越多的科研证据表明,危害人类健康的心血管疾 病尧糖尿病尧肥胖症以及癌症等与膳食有着不解之缘遥 根据美国的一项统计,超过 80%的患者的死亡原因 与上述几种疾病密不可分遥 血脂的含量与这些疾病的发生密切相关, 而血脂的高低又受到膳食中脂类物 质的成分及人们摄入脂类物质量的影响遥 如今西化的膳食习惯,导致人们脂肪总摄入量大大增加,此外,膳 食中 n-6 多不饱和脂肪酸(n-6 PUFAs)过量,n-3 PUFAs 严重不足,n-6/n-3 比例的失衡也是多种疾病发生 的潜在危险因素遥 目前,有关 n-3 PUFAs 对心血管疾病尧癌症尧肥胖尧糖尿病等疾病的预防作用的研究广泛 而深入,但环境对基因的作用如何,尤其是对于人体健康而言,膳食与基因存在怎样的相关性,彼此之间是 如何相互作用,相关的研究报道较少遥 现有的动物实验结果提示,膳食中脂肪的量和成份严重影响着动物 的健康,对于具有不同遗传背景以及遗传易感性的人群而言,膳食可能对基因发生的影响力,但目前尚无 明确定论遥 本文主要综述了 n-3 PUFAs 的膳食来源,在人体的代谢情况,及 n-3 PUFAs 在肿瘤防治尧临床 试验和治疗中的作用遥 一尧n-3尧n-6 PUFAs 的膳食来源 人体可以从头合成或从食物中摄取多种饱和及单不饱和脂肪酸遥 但哺乳动物缺乏合成 n-3尧n-6 PU鄄 FAs 的脱氢酶,因此这些必需脂肪酸只能从食物中摄取遥 陆生植物可以合成 n-6 系列 PUFAs 的第 1 个成员要要 要亚油酸(LA;18颐 2n-6)遥 几乎所有食用植物油如 玉米油尧 葵花油尧 红花油尧 橄榄油中 LA 的含量都很丰富遥 植物也能合成 n-3 系列 PUFAs 的第一个成 员要要 要琢 -亚麻酸(琢 -LNA,18颐 3 n-3),富含 琢 -LNA 的植物包括大豆尧核桃尧深绿色叶蔬菜如甘蓝尧菠菜尧椰 菜尧抱子甘蓝的种子等,一些油类如亚麻子油尧芥菜籽油尧菜籽油中,琢 -LNA 的含量也很丰富,同时也富含大 量 LA遥 膳食中的长链 n-3 PUFAs 主要以二十碳五烯酸(EPA,20颐 5 n-3)和二十二碳六烯酸(DHA,22颐 6 n-3) 的形式储存于冷水鱼体内遥 鱼类可以从浮游植物和浮游动物中摄取 EPA 和 DHA,不同种类尧栖息在不同 水域的鱼类,体内总脂肪及 n-3 PUFAs 的含量变化很大即便同一种类的鱼,生活在大西洋和太平洋,体内 n-3 PUFAs 含量的差异也很大遥 总之,深海冷水鱼如鲭鱼尧金枪鱼尧鲑鱼等,含 DHA 和 EPA 的量最高遥 人工 饲养的鱼类,喂食不同的饲料,其体内脂肪酸的组成也有显著区别遥 二尧n-3尧n-6 PUFAs 在人体内的代谢 虽然哺乳动物不能从头合成 n-3尧n-6 PUFAs,但哺乳动物细胞可以通过碳链的延长尧去饱和作用和逆 转等方式使 PUFAs 之间发生转化 [1] 遥 摄食后,LA 通过一系列氧化去饱和及碳链延长的交替作用被代谢,生 成花生四烯酸(AA,20颐 4 n-6)遥PUFAs 转化的主要代谢途径见图 1遥驻 6 途径负责 LA 转化为 AA,琢 -LNA 转化 为 EPA,这个步骤主要在肝脏细胞的内质网中进行遥驻 8 途径主要存在于植物中,可以生成 AA 与 EPA,但是 灶-猿 多不饱和脂肪酸与恶性肿瘤 杨婷 余红兰 石汉平 530 窑 窑

哪些食物含有丰富的不饱和脂肪酸

哪些食物含有丰富的不饱和脂肪酸 不饱和脂肪酸是脂肪酸的一部分,其中包括:单不饱和脂肪酸和多不饱和脂肪酸。不饱和脂肪酸和饱和脂肪酸在化学结构上有显著区别,饱和脂肪酸的碳原子链上没有不饱和键,而单不饱和脂肪酸(MUFA)碳原子链上含有一个不饱和键,多不饱和脂肪酸(PUFA)碳原子链上含有多个不饱和键。 脂肪酸是脂肪的基本结构,自然界的脂肪酸有40多种。食物中脂肪来源于植物性脂肪和动物性脂肪。一般来讲,猪油、奶油、牛油等动物性脂肪含饱和脂肪酸为主,植物性油脂则主要含不饱和脂肪酸为主。在多不饱和脂肪酸中,有重要生物学意义的是n-3和n-6系列。n-3和n-6系列包括亚麻酸(LA)、花生四稀酸(AA)、二士碳五稀酸(EPA)、二十二碳六稀酸(DHA)、二十二碳五稀酸(DPA)等,他们对婴儿脑、神经发育产生重要影响。 婴幼儿正处于大脑神经发育的第二个高峰期,n-3和n-6系列不饱和脂肪酸对婴幼儿脑发育的促进已得到公众认可,他们的生理作用有(1)促进神经组织发育过程中核酸和新蛋白合成,参与神经细胞膜磷脂及线粒体合成,促进突触结构发育和神经纤维髓鞘化过程,(2)调节神经递质活性,加快神经传导速度。(3)有利于小儿视网膜发育(4)增进免疫功能调节(5)降低血脂减少心血管疾病发生。 含多不饱和脂肪酸的食物有:母乳、豆油、葵花籽油、核桃油、红花油、大豆色拉油和坚果类食物。近年来许多婴儿奶粉厂商采用高科技手段在婴儿配方奶粉中强化了一定比例的DHA、ARA等营养素,从而解决了牛乳中缺乏多不饱和脂肪酸影响婴儿脑发育的问题。从鱼油或海藻中提炼出来的多不饱和脂肪酸制剂或营养保健品也可以成为我们补充多不饱和脂肪酸的选择。世界卫生组织建议;人体每天摄入多不饱和脂肪酸的总量要占到总能量的6-10%,其中n-3脂肪酸建议摄入量占总能量的1-2%,n-6脂肪酸的摄入量占5-8%。 多不饱和脂肪酸对婴儿的健康发育有重要影响,但并不能否认单不饱和脂肪酸和饱和脂肪酸的生理功能,从营养学角度,并不存在好脂肪和坏脂肪的概念,我们应该科学合理的摄取各种营养素。 三鹿营养专题提供

不饱和脂肪酸

EPA 二十碳五烯酸,是鱼油的主要成分。虽然亚麻酸在人体内可以转化为EPA,但此反应在人体中的速度很慢且转化量很少,远远不能满足人体对EPA的需要,因此必须从食物中直接补充。 作用 1、治疗自身免疫缺陷。 2、促进循环系统的健康。Ω-3脂肪酸已经被证实能促进循环系统的健康和防止胆固醇和脂肪在动脉壁上积聚 3、有助于生长发育。保持身体里的Ω-3脂肪酸含量处于一个适当平衡的位置对正常的生长和发育是十分必要的。营养专家建议婴儿应从日常饮食和补充剂中吸收各种类型的Ω-3脂肪酸。根据这些建议的要求,婴儿在日常饮食中吸收的EPA应少于 0.1%。 4、其他的情况。Ω-3脂肪酸,包括EPA在内,对肺病、肾病、2型糖尿病、大肠溃疡和节段性回肠炎的治疗都会起到积极的作用。 5、EPA具有帮助降低胆固醇和甘油三酯的含量,促进体内饱和脂肪酸代谢。从而起到降低血液粘稠度,增进血液循环,提高组织供氧而消除疲劳。防止脂肪在血管壁的沉积,预防动脉粥样硬化的形成和发展、预防脑血栓、脑溢血、高血压等心血管疾病。 6、DHA与EPA组合具有保护眼睛,提高视网膜的发射机能作用。国家卫生部要求:DHA与EPA的配比必须在二点五比一以上。 参考摄入量 中国营养学会副理事长苏宜香教授表示,“相关研究已证实了DHA和EPA对人类的健康有更多益处”。 据联合国粮农组织专家委员会联合会商提出的报告显示,每日摄取250—2000毫克的EPA与DHA是构成人类健康饮食的重要组成部分。报告还指出,“成年男性和非孕期或哺乳期女性每天食用250毫克DHA+EPA; 目前中国成年人人均每天DHA+EPA摄入量仅有37.6毫克,不到美国医学研究院建议值(160mg/天)的四分之一,据国家权威调查数据分析显示,属严重缺乏状态。就是这样一个身体状况,对迎接宝宝的身体准备是不足的,据联合国粮农组织专家委员会联合会商提出的报告显示,孕期和哺乳期女性每日摄取DHA+EPA300毫克,是保证母亲和婴儿最佳健康发育水平的最低标准”。[3] 母乳中DHA:AA的配比均衡,帮助DHA和AA共同吸收,对0-6个月宝宝的头脑智力发育至关重要: 根据研究,中国妈妈母乳中DHA:AA的平均比例约为1:1.7,过多的DHA会抑制AA的吸收 实验证明-相比单独作用,DHA和AA共同作用更有利于支持宝宝脑部发育。 DHA/AA配比(1:1-1:2)亲和人体:帮助DHA和AA的有效利用;

橄榄油中的单不饱和脂肪酸功能

要让低密度脂蛋白的含量降下来,最理想的办法是提升高密度脂蛋白的含量。高密度脂蛋白在血管中起着两个至关重要的作用。一是保护作用,能防止低密度脂蛋白在血管上的沉积,并能修复受损的血管内膜;二是清洁作用,高密度脂蛋白会将黏附在血管壁上的低密度脂蛋白等“垃圾”铲除下来,并携带到肝脏中去进行分解代谢,最终排出体外,从而达到降低人体内胆固醇含量的作用,是机体内唯一的抗动脉硬化的血管保护因子,因而高密度脂蛋白被誉为“血管的清道夫”。单不饱和脂肪酸能有效提升高密度脂蛋白在机体内的含量,能有效地降低人体中胆固醇的含量,因此长期摄入富含单不饱和脂肪酸的橄榄油,能有助于抑制心脑血管疾病的形成。 1.单不饱和脂肪酸的抗氧化功能 多不饱和脂肪酸可以调整人体的各种机能,有清除人体内代谢的“垃圾”等一系列有益于健康的作用。但是多不饱和脂肪酸也有一个最大的缺点,那就是怕氧化。作为植物油的多不饱和脂肪酸,一旦被氧化,就会演变成过氧化物。过氧化物与蛋白质结合,那么就会形成可怕的脂褐素,这是可以引起人的衰老、心血管疾病及老年痴呆症的有害物质,因此摄入不饱和脂肪酸还应同时考虑抗氧化的问题。而同属不饱和脂肪酸的单不饱和脂肪酸却有着得天独厚的抗氧化功能,其中最为突出的代表是橄榄油。以地中海地区的希腊克里特岛居民的脂肪摄入为例,他们的脂肪热量占总热量的比例高达40%,照理来说这样高的脂肪摄入,会导致冠心病高发。然而,令人难以置信的是,克里特岛居民的冠心病、脑卒中、癌症及糖尿病等疾病的发病率却相当低,他们的寿命较长,而且生命质量也相当好。原因是什么呢?通过大量的实地调查,发现克里特岛居民奉行地中海膳食模式,其中大量的脂肪的摄入主要是富含单不饱和脂肪酸的橄榄油。橄榄油由于采取冷榨处理,油脂中保留了抗氧化的成分,因此,橄榄油没有其他不饱和脂肪酸易被氧化的后顾之忧,也不会出现过氧化物质。 2、单不饱和脂肪酸的降血糖功能 科学家们经过研究发现,含高单不饱和脂肪酸的橄榄油,能够降低Ⅱ型糖尿病患者的血糖水平,尤其对餐后血糖水平的降低更加明显,在临床上比标准配方的营养制剂更能适合于糖尿病患者的营养需求。

DHA+与+EPA+合成超长链多不饱和脂肪酸的效率比较

【通讯作者】吴峥峥 DHA与EPA合成超长链多不饱和脂肪酸的效率比较 余 曼,陈 波,张瑞帆,吴峥峥 (四川省医学科学院?四川省人民医院眼科,四川成都610072) 【摘要】 目的 比较在ELOVL4蛋白酶催化作用下,DHA和EPA合成超长链多不饱和脂肪酸VLC-PUFA的效率。方法 构建携带ELOVL4基因和绿色荧光蛋白的重组腺病毒,转入培养的PC12细胞,通过qRT-PCR定量分析ELOVL4基因的表达量,WB检测ELOVL4蛋白的表达;1∶1加入DHA和EPA,孵育48h之后进行脂肪酸提取,通过气相质谱GC-MS分析超长链脂肪酸的成分。结果 GC-MS检测到分别用DHA及EPA处理后的PC12+Ad-ELOVL4的细胞中有n3VLC-PUFA的表达,34:5n3和36:5n3分别为0畅85%和1畅11%;34:6n3和36:6n3分别为0畅16%和0畅29%;EPA所产生的五烯酸总和是DHA所产生的六烯酸总和的4倍。结论 EPA合成VLC-PUFA的效率远远高于DHA,为患者提供更高比例的EPA,而非DHA,可能是治疗STGD3疾病的方式之一。 【关键词】 二十二碳六烯酸;二十碳五烯酸;ELOVL4基因;Stargardt病;超长链多不和脂肪酸【中图分类号】R77 【文献标志码】A 【文章编号】1672-6170(2014)05-0024-04 ComparisonofelongationefficiencybetweenDHAandEPAinsynthesisofverylongchainpolyunsaturatedfattyacids YUMan,CHENBo,ZHANGRui-fan,WUZheng-zheng (DepartmentofOph- thalmology,SichuanAcademyofMedicalSciences&SichuanProvincialPeople摧sHospital,Chengdu610072,China) 【Correspondingauthor】 WUZheng-zheng 【Abstract】 Objective TocomparetheelongationefficiencybetweenDHAandEPAforsynthesisofverylongchainpolyunsat-uratedfattyacid(VLC-PUFAs)undercatalyticactionofELOVL4protease.Methods PC12cellsweretransducedwithrecombinantadenovirustype5carryingmouseElovl4andgreenfluorescentprotein(GFP).GFP-expressingandnon-transducedcellswereusedascontrols.ELOVL4geneexpressionwasquantifiedbyqRT-PCRs.ELOVL4proteinwasanalyzedbyWestern-Blot(WB).ThetransducedcellsweretreatedwithDHAorEPA(1:1).After48hofincubation,cellswerecollected,andfattyacidmethylesterswerepreparedfollowingtotallipidsextraction.Thefattyacidwasanalyzedbyusingagaschromatography-massspectrometry(GC-MS).Results GC- MSanalysisshowedthattheDHAandEPAtreatedPC12+ Ad-ELOVL4hadn3VLC-PUFAsinwhich34:5n3and36:5n3were0畅85%and1畅11%,respectively;34:6n3and36:6n3were0畅16%and0畅29%,respectively.TotalamountofpentaenoicssynthesizedfromEPAwasalmostfourtimesthanthatofhexaenoicssynthesizedfromDHA.Conclusion ElongationefficiencyofVLC-PUFAsfromEPAismuchhigherthanthatfromDHA.Therefore,dietarysupplementationofmoreEPAratherthanDHAmayprovidesometherapeuticbenefitsforpatientswithStargardts摧disease(STGD3). 【Keywords】 Docosahexaenoicacid(DHA),Eicosapentaenoicacid(EPA),ELOVL4gene,Stargardts摧disease,Verylongchainpolyunsaturatedfattyacid(VLC-PUFA) 以DHA和EPA为代表的n3PUFAs(polyunsat-uratedfattyacids,PUFAs)是指含有两个或两个以上双键的一类脂肪酸,通常按照第一个双键的位置把多不饱和脂肪酸分类,其中n3PUFAs,即从甲基端数第1个双键的位置在第3碳位的多不饱和脂肪酸,如二十二碳六烯酸(22:6n3,DHA)和二十碳五烯酸(20:5n3,EPA)。在哺乳动物神经系统中,n3PUFAs不但是重要的结构组分,而且是重要的营养 因子[1] 。DHA被认为是功能最强的n3PUFAs, DHA与人类多种神经性疾病,例如阿尔默茨症[2] 。 Stargardt病(Stargardt-likemaculardystrophy,STGD)是一种发生于青少年期的遗传性黄斑营养不良,目前尚无有效的治疗方法。近年来的研究又发现,ELOVL4基因第VI外显子上突变导致了人类的 常染色体显性遗传STGD3的发病[3] 。ELOVL4属 于超长链脂肪酸延伸酶(elongaseofELOngationofverylongchainfattyacids,ELOVL)家族,已被证实参与多不饱和脂肪酸(verylongchainPUFA,VLC-PU- FA)的C28-C38碳链延长的生化过程[4] 。McMahon等发现,ELOVL4基因突变的STGD3小鼠模型的视 网膜中的C32-C36酰基磷脂酰胆碱的水平下降[5] ,VLC-PUFA水平减少还会导师ERG波幅的下降,因此,治疗STGD3的策略之一可能是通过食物供给方式将VLC-PUFA送到视网膜组织。然而,由于VLC-PUFA结构的不稳定性,使得其很能被大量生产,那么另外一种方式就是通过提供VLC-PUFA的前体物质,体内合成VLC-PUFA。图1显示n3PUFAs的合成通路,我们看到DHA和EPA均为VLC-PUFA的前体脂肪酸,尤其是DHA占有在感光体外部节段磷 脂中大约50%的脂肪酸[6] ,它在神经系统以及视网膜中的作用曾受到广泛的关注。本研究将转基因ELOVL4蛋白在PC12细胞中过量表达,等浓度加入 4 2 实用医院临床杂志2014年9月第11卷第5期

多不饱和脂肪酸的生理功能及安全性.

多不饱和脂肪酸(Polyunsaturatedfattyacids,PUFA)是指含有两个或两个以上双键且碳链长为18~22个碳原子的直链脂肪酸,是研究和开发功能性脂肪酸的主体和核心,主要包括亚油酸(LA)、γ-亚麻酸(GLA)、花生四烯酸(AA)、二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)等。其中,亚油酸及亚麻酸被公认为人体必需的脂肪酸(EA),在人体内可进一步衍化成具有不同功能作用的高度不饱和脂肪酸,如AA、EPA、DHA等。 多不饱和脂防酸因其结构特点及在人体内代谢的相互转化方式不同,主要可分为ω-3、ω-6两个系列。在多不饱和脂肪酸分子中,距羧基最远端的双键在倒数第3个碳原子上的称为ω-3多不饱和脂肪酸,如在第6个碳原子上,则称为ω-6多不饱和脂肪酸[1]。 1多不饱和脂肪酸的生理功能 多不饱和脂肪酸不仅因为ω-6系列的亚油酸和ω- 3系列的亚麻酸是人体不可缺少的必需脂肪酸,更重要的是因为由它们在体内代谢转化或者特定食物资源中摄入的几种多不饱和脂肪酸,在人体生理中起着极为重要的作用。 1.1不饱和脂肪酸与心血管系统疾病 多不饱和脂肪酸对动脉血栓形成和血小板功能有明显影响。亚油酸的摄入量与血浆磷脂、胆固醇酯和甘油三酯中的亚油酸含量有很强的相关关系,而且血小板的总亚油酸、α-亚麻酸、花生四烯酸、EPA,以及DHA与血浆甘油三酯、磷脂、脂肪组织中的脂肪酸浓度呈显著相关性。在芬兰进行的两项研究发现,ADP诱导的血小板聚积与脂肪组织和血浆甘油三酯中的亚油酸含量呈显著正相关,但与血小板的亚油酸含量无相关关系。γ- 亚麻酸在临床上的试验结果表明有降血脂作用,对甘油三酯、胆固醇、β-脂蛋白的下降有效性在60%以上,而且,γ-亚油酸在体内转变成具有扩张血管作

转基因植物生产超长链多不饱和脂肪酸研究进展

植物学通报 Chinese Bulletin of Botany 2007, 24 (5): 659?666, https://www.wendangku.net/doc/7817890910.html,
.专题介绍.
转基因植物生产超长链多不饱和脂肪酸研究进展
石娟, 朱葆华, 潘克厚 *
中国海洋大学海水养殖教育部重点实验室, 青岛 266003
摘要
超长链多不饱和脂肪酸(VLCPUFAs)对人类健康非常重要。日常摄入一定量的VLCPUFAs能够补充人体自身合成的
不足, 并对某些疾病起到明显的预防和治疗作用。VLCPUFAs主要源自深海鱼油, 但由于市场需求的迅速增长和海洋可捕捞 鱼类资源的日益减少, 该途径已经远远不能满足市场的需要, 寻找更为持续且稳定的VLCPUFAs来源已经成为当务之急。最 近, 人们已经克隆了VLCPUFAs生物合成相关的去饱和酶和延伸酶基因, 并希望在植物特别是油料作物中共表达这些基因, 使 其成为生产VLCPUFAs的 “绿色细胞工厂” 。目前已有多个研究小组在进行转基因植物合成VLCPUFAs的探索, 并取得了突 破性的研究成果。本文综述了相关的研究进展, 并对存在的问题和解决策略进行了探讨。
关键词 DHA, EPA, 转基因植物, 超长链多不饱和脂肪酸
石娟, 朱葆华, 潘克厚 (2007). 转基因植物生产超长链多不饱和脂肪酸研究进展. 植物学通报 24, 659?666.
超长链多不饱和脂肪酸(VLCPUFAs)是指含有 20 或 22个碳原子及4-6个亚甲基间隔的顺式双键的脂肪 酸链(Abbadi et al., 2004), 包括花生四烯酸(AA, 20: 4n6)、 二十碳五烯酸(EPA, 20:5n3)和二十二碳六烯酸 (DHA, 22:6n3)。 多不饱和脂肪酸(PUFAs)可分为n6系 列和 n3 系列。AA 属于 n6 PUFAs; EPA 和 DHA 属于 n3 PUFAs。 研究表明, VLCPUFAs 对人类健康非常重 要。AA 和 EPA 是哺乳动物细胞膜的组分, 也是生成前 列腺素、白三烯和血栓素等激素的前体(Funk, 2001)。 EPA 在凝血、免疫和抗炎症等各种生理反应中起重要 作用(Simopoulos, 2002)。DHA 对胎儿神经系统的形 成至关重要(Uauy et al., 2001), 还影响着视网膜视紫 红质的活性(Giusto et al., 2000), 并与某些疾病如关节 炎、动脉硬化、抑郁症的预防和治疗有关(Horrocks and Yeo, 1999; Marszalek and Lodish, 2005)。 人体合成 EPA 和 DHA 的效率极低, 在日常饮食中
补充足够的 EPA 和 DHA 对维持身体健康极为重要。 目 前该类脂肪酸的主要来源是深海鱼油, 但是鱼类自身并 不能合成 VLCPUFAs, 而是通过摄食富含 VLCPUFAs 的海藻等进行有限的积累; 另外, 过度捕捞使海洋鱼类资 源日益减少, 该途径已经远远不能满足迅速增加的市场 需求。 此外, 由于环境污染等原因导致鱼油中的重金属 含量越来越高, 寻找更为持续、稳定、安全的 EPA 和 DHA来源成为当务之急(Tonon et al., 2002; Domergue et al., 2005a)。已知某些微生物如真菌和海洋微藻能 够从头合成 VLCPUFAs 且含量丰富(Sayanova and Napier, 2004); 然而现已开发出的商业化的海藻油和真 菌油, 由于其产量低和提取成本高限制了这类资源的大 规模应用。 鉴于植物油的提取工艺非常成熟, 许多研究 者已经将目光转向油料作物的代谢工程, 探索如何利用 转基因植物作为 “绿色细胞工厂 ”生产 V LC PU FA s (Truksa et al., 2006)。近年来国外一些研究小组已在
收稿日期: 2006-10-24; 接受日期: 2007-04-09 基金项目: 973 重大基础研究前期研究专项(No. 2005CCA02400) * 通讯作者。E-mail: khpan@https://www.wendangku.net/doc/7817890910.html, 缩写词: AA: arachidonic acid; ALA: α-linolenic acid; DGLA: dihomo-γ-linolenic acid; DHA: docosapentaenoic acid; EDA: eicosadienoic acid; EPA: eicosapentaenoic acid; ER: endoplasmic reticulum; ETA: eicosatetraenoic acid; GLA: γ-linolenic acid; LA: linoleic acid; LPCAT: lyso-phosphatidycholine acyltransferase; OA: oleic acid; PC: phosphatidycholine; PDAT: phospholipid diacylglycerol acyltransferase; PUFAs: polyunsaturated fatty acids; SDA: stearidonic acid; TAG: triacylglycerol; TPA: tetracosapentaenoic acid; VLCPUFAs: very long-chain polyunsaturated fatty acids

多不饱和脂肪酸功能和应用综述

编号 食品分离技术(综述)题目:多不饱和脂肪酸功能与应用综述食品学院营养与卫生学专业 班级食硕1005 学号s100109030 学生姓名张锦 二〇一一年一月

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单不饱和脂肪酸的作用

单不饱和脂肪酸的作用 和DHA(OMEGA-3),这两者都是常见的多元不饱和脂肪酸。它们对我们的心血管起保护作用,而且也有益于大脑的健康。值得一提的是我们大脑的60%是由脂肪材料构成,神经的生长需要必需脂肪酸作为原材料。对神经和神经元的机能来讲,需要必需脂肪酸提供能量。对于学生来说,大脑中应有足够的DHA,否则,即使刻苦学习,大脑细胞也得不到良好的刺激及生长发育,因此必须摄入足量的紫苏油,这样才能有效地提高学习成绩。对于孕妇与幼儿也有健脑效果,如果孕妇缺少DHA,胎儿脑细胞数必然不足,严重时会引起弱智或流产。所以孕妇在妊娠时能长期补充DHA(紫苏油),通过母体将DHA输送到胎儿大脑,对胎儿大脑的初期发育起到关键作用。必需脂肪酸能促进核酸、蛋白质生成,帮助神经传导和促成神经突触生长、分化、成熟,对婴儿生长发育起着重要作用。如果人体缺乏必需脂肪酸会导致神经系统紊乱,从而情绪低落,麻痹,掌控能力失调和加速衰老。 二、预防心脏疾病,老年性痴呆心脏疾病是人类的第一号杀手,α-亚麻酸可降低中风的机率和心脏病的突发,预防乳癌和肠癌。α-亚麻酸可降低70%心脏病突发的风险。紫苏油中含有丰富的α-亚麻酸-OMEGA-3,它是我们人类一生需求的脂肪酸。老年性痴呆,动脉粥样硬化,心脏瓣膜的疾病甚至癌症,都是由于炎症间接引起的,老化也是体内炎症所致。必须脂肪酸可以控制慢性炎症,却没有副作用。 三、治疗风湿关节炎研究证明,OMEGA-3必需脂肪酸可以有效地

治疗风湿性关节炎和其它的一些炎症。 四、预防和治疗前列腺疾病前列腺素是我们体内生化合成的一种类似荷尔蒙的物质,它有正作用也有副作用,体内过多的饱和脂肪酸形成前列腺素E2,它促进炎症的扩散,α-亚麻酸可产生前列素E3,它能抑制E2的生成。大量坏的脂肪酸滋生肿瘤细胞,常常产生大量的前列腺素E2,同时降低免疫系统让肿瘤细胞能够躲过免疫防线,一些癌细胞支配前列腺素E2的产生促进肿瘤细胞的增殖。OMEGA-3必须脂肪酸可以降低前列腺素E2产生的风险,维持体内脂肪酸的平衡。 据文献报道,英国专家发现并分离出了导致癌症患者身体消瘦的一种物质,而且还惊奇发现这一物质的活动受到紫苏油控制。 这种名叫长奇非克因小的物质类似荷尔蒙,是由某些顽固的肿瘤所产生的,它利用脂肪来供给肿瘤,促使肿瘤的生长,从而使患者身体消瘦。而二十碳五烯酸(EPA)这种物质能控制长奇非克因小的活动,从而控制癌症患者的消瘦,还能使肿瘤缩小。此外,日本有人用紫苏油与其它油做抗大肠菌的对比实验,证明紫苏油抑制肿瘤的作用强于红花油,豆油。 传统摄取不饱和脂肪酸三种途径比较1、传统的鱼油 2、亚麻子油中的OMEGA-3 3、紫苏油传统的鱼油和亚麻子油中的OMEGA-3有引起肠道不适的副作用。但是紫苏油没有此副作用。深海鱼油可降低冠状动脉硬化的风险,除此之外鱼油还能限制非正常血小板凝聚和防止心脏病突发和血栓形成,预防中风。而在这点上,紫苏油比鱼油具有

饱和脂肪酸与不饱和脂肪酸有什么区别

摘自:“营养健康教育指南”北京市营养源研究所蒋峰主编 脂肪是由一个甘油分子支架和连接在其支架上的三个分子的脂肪酸组成,其中甘油的分子结构比较简单,而脂肪酸的种类和长短却各不相同,因此脂肪的性能和作用主要取决于脂肪酸。 脂肪酸是脂肪分子的基本单位,而每一种脂肪酸在结构上则有很大的差异,根据其结构不同可分为三大类:饱和脂肪酸、单不饱和脂肪酸和多不饱和脂肪酸。(一)饱和脂肪酸 饱和脂肪酸的主要来源是家畜肉和乳类的脂肪,还有热带植物油(如棕榈油、椰子油等),其主要作用是为人体提供能量。它可以增加人体内的胆固醇和中性脂肪;但如果饱和脂肪摄入不足,会使人的血管变脆,易引发脑出血、贫血、易患肺结核和神经障碍等疾病。单不饱和脂肪酸 (二)单不饱和脂肪酸 单不饱和脂肪酸主要是油酸,含单不饱和脂肪酸较多的油品为:橄榄油、芥花籽油、花生油等。它具有降低坏的胆固醇(LDL),提高好的胆固醇(HDL)比例的功效,所以,单不饱和脂肪酸具有预防动脉硬化的作用。 (三)多不饱和脂肪酸 多不饱和脂肪酸虽然有降低胆固醇的效果,但它不管胆固醇好坏都一起降,且稳定性差,不适合加热,在加热过程中容易氧化形成自由基,加速细胞老化及癌症的产生。 多不饱和脂肪酸主要是亚油酸、亚麻酸、花生四烯酸等;其中亚油酸、亚麻酸为必需脂肪酸。含多不饱和脂肪酸较多的油有:玉米油、黄豆油、葵花油等等。 1.亚油酸的作用 亚油酸是人体必需脂肪酸,它具有预防胆固醇过高、改善高血压、预防心肌梗死、预防胆固醇造成的胆结石和动脉硬化的作用。 但是,如果亚油酸摄取过多时,会引起过敏、衰老等病症,还会抑制免疫力、减弱人体的抵抗力,大量摄取时还会引发癌症。 表3-3 富含亚油酸的食物(克/100克) 名称亚油酸含量名称亚油酸含量

不饱和脂肪酸对健康的影响

不饱和脂肪酸与人体健康关系探讨 摘要:本文系统的介绍了各种不饱和脂肪酸对人体健康的有利和不利影响,为人们合理的摄取油脂提供了科学依据。 关键词:长链多不饱和脂肪酸;共轭脂肪酸;反式脂肪酸;健康 膳食中油脂的来源主要有动物性脂肪和植物油,陆生动物脂肪的脂肪酸三甘油酯含高比例的饱和脂肪酸,室温下呈固态;绝大部分植物油的脂肪酸三甘油酯含较多不饱和脂肪酸,室温下呈液态;某些海洋鱼油中,其脂肪酸三甘油酯含高比例多不饱和脂肪酸,室温下也呈液态?。食品脂质中的不饱和脂肪酸的双键大都是顺式构型,氢原子在双键的同一侧,植物油氢化后熔点提高,氢化过程在加热、加压、通氢气和催化剂存在下进行,部分氢化能使脂肪酸的顺式双键转变为反式构型,反式酸键角小,致使熔点升高,食品中反式酸主要来自氢化植物油为基料制成的人造奶油和起酥油[1]。 1 不饱和脂肪酸对人体健康的影响 1.1 长链多不饱和脂肪酸对人体健康的影响 长链多不饱和脂肪酸(简称LCPUFAs)又叫多烯酸,是指分子结构中含有两个或两个以上不饱和双键且碳原子数目在20个以上的脂肪酸。与人体健康密切相关的多不饱和脂肪酸主要有两类:一类是n-3系多不饱和脂肪酸(n-3PUFAs);另一类是n一6系多不饱和脂肪酸(n一6PUFAs)。前者主要包括一亚麻酸、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA);而后者主要包括亚油酸、v一亚麻酸和花生四烯酸,它是生长发育、生殖及保持皮肤健康所必需的[2]。营养学家在研究脂质对人类健康影响时,发现膳食及体内保持一定的n一6PUFAs/n一3PUFAst:g例平衡很重要。PUFAs与类脂质结构、代谢及精子的形成等有关。 多不饱和脂肪酸是组成组织细胞生物膜必不可少的成份,它在体内参与磷脂的合成,并以磷脂的形式出现在线粒体和细胞膜中。 1.1.1 n一3PUFAs对人体的生理作用 对心血管系统:多项研究表明,i"1—3PUFAsH‘L够促进人体防御系统功能,使血液中的脂肪酸谱向着对人体健康有利的方向发展,能抑制血栓形成,降低血脂,

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