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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.河北,石家庄 050051

摘要

该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、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（{sl 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（{sl 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Rmax均比孵育前增加，经N~(#omega#)--吐硝基--L--精氨酸（N~(#omega#)--nitro--L--arginine，L--NNA）及美蓝（methyleneblue，MB）孵育后，两高脂组Rmax均比孵育前降低（{sl P}<0.05，{sl P}<0.01）；对照组各孵育液之间无显著性差异（{sl 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（{sl 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

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 Guangyao, Ma Huijuan, Zhang Wenjie, Zhou Yu

Department of Geriatrics, Hebei Provincial People's Hospital, Hebei Provinical Geriatric Key Laboratory.Shijiazhuang 050051,Hebei

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 triglyceride （TG）, free fatty acid （FFA）, 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~(#omega#)-nitro-L-arginine （L-NNA） and methylene blue （MB）, respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 #mu#mol/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 decreased 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

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引用本文：

高宇, 宋光耀, 马慧娟, 张文杰, 周宇. 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[J]. 生理学报 2007; 59 (3): 363-368.

Gao Yu, Song Guangyao, Ma Huijuan, Zhang Wenjie, Zhou Yu. Effects of long--term high--saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats. Acta Physiol Sin 2007; 59 (3): 363-368 (in Chinese with English abstract).