Palmer A M, Gopaul N, Dhir S, Thomas C R, Poston L, Tribe R M
Division of Obstetrics and Gynaecology, United Medical and Dental Schools, St Thomas' Hospital, London, UK.
Diabetologia. 1998 Feb;41(2):157-64. doi: 10.1007/s001250050884.
Oxidative stress and dyslipidaemia are key features of diabetes mellitus and may be involved in mediating the vascular endothelial dysfunction associated with this disease. The aim of this study was to examine the effect of dietary lipid-lowering and antioxidant agents on vascular endothelial function and oxidative stress. Diabetic male Sprague-Dawley rats (i.v. streptozotocin, 45 mg/kg) were fed for 4 weeks on a standard diet or on a diet supplemented with either the lipid-lowering antioxidant probucol (1% w/w in diet) or the 3-hydroxy 3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor simvastatin (0.01% w/w in diet). Responses to noradrenaline, acetylcholine, and sodium nitroprusside were assessed in small mesenteric arteries (mean internal diameter 300+/-5 microm, n = 80) mounted on a small vessel myograph. Plasma concentrations of total cholesterol and triglycerides were significantly raised in standard-fed diabetic rats and significantly reduced in probucol and simvastatin-fed diabetic rats 8-epi-prostaglandin (PG)F2alpha, an indicator of oxidative stress, was raised in liver and aorta from diabetic rats compared to controls. Probucol supplementation reduced 8-epi-PGF2alpha in aorta and liver of diabetic rats but increased 8-epi-PGF2alpha content in plasma and aorta from control animals. The abnormal relaxation to acetylcholine in arteries from the diabetic rats (pEC550 diabetic 6.763+/-0.172 vs control 7.541+/-0.175; p < 0.05) was not improved by probucol or simvastatin. These data, therefore, do not support a role for oxidative stress or dyslipidaemia in mediating the impaired ACh-induced endothelium-dependent relaxation of small mesenteric arteries from the streptozotocin-diabetic rat.
氧化应激和血脂异常是糖尿病的关键特征，可能参与介导与该疾病相关的血管内皮功能障碍。本研究的目的是检查饮食中的降脂和抗氧化剂对血管内皮功能和氧化应激的影响。将雄性糖尿病Sprague-Dawley大鼠（静脉注射链脲佐菌素，45mg/kg）以标准饮食喂养4周，或以补充了降脂抗氧化剂普罗布考（饮食中1%w/w）或3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂辛伐他汀（饮食中0.01%w/w）的饮食喂养4周。在安装在小型血管肌动描记器上的小肠系膜小动脉（平均内径300±5μm，n = 80）中评估对去甲肾上腺素、乙酰胆碱和硝普钠的反应。标准饮食喂养的糖尿病大鼠血浆总胆固醇和甘油三酯浓度显著升高，而普罗布考和辛伐他汀喂养的糖尿病大鼠则显著降低。与对照组相比，糖尿病大鼠肝脏和主动脉中氧化应激指标8-表前列腺素（PG）F2α升高。补充普罗布考可降低糖尿病大鼠主动脉和肝脏中的8-表PGF2α，但会增加对照动物血浆和主动脉中的8-表PGF2α含量。糖尿病大鼠动脉对乙酰胆碱的异常舒张（pEC50糖尿病大鼠为6.763±0.172，对照组为7.541±0.175；p < 0.05）未被普罗布考或辛伐他汀改善。因此，这些数据不支持氧化应激或血脂异常在介导链脲佐菌素诱导的糖尿病大鼠小肠系膜小动脉乙酰胆碱诱导的内皮依赖性舒张受损中起作用。
