Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats
Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats
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DOI：
10.1038/sj.bjp.0703572
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发表时间：
2000-09-01
影响因子：
7.3
通讯作者：
Kamata, K
中科院分区：
文献类型：
--
作者：
Kobayashi, T;Matsumoto, T;Kamata, K
1我们研究了普伐他汀对链脲佐菌素（STZ）诱导的糖尿病大鼠血管内皮依赖性舒张功能的影响。从糖尿病6周开始，对STZ诱导的糖尿病大鼠给予普伐他汀（10 mg kg（-1））4周。2在STZ诱导的糖尿病大鼠中观察到的总胆固醇和低密度脂蛋白（LDL）胆固醇水平升高，普伐他汀不能使其恢复正常。普伐他汀治疗的糖尿病大鼠的主动脉对乙酰胆碱的内皮依赖性舒张未表现出受损。内皮型一氧化氮合酶的mRNA表达不受糖尿病或普伐他汀的影响。3在STZ诱导的糖尿病大鼠中观察到的丙二醛（MDA）修饰的LDL水平升高通过普伐他汀治疗恢复正常。通过测量与铜离子孵育产生的MDA或共轭二烯的量来评估LDL对氧化的抗性。从糖尿病大鼠中分离的LDL，而不是从普伐他汀治疗的糖尿病患者中分离的LDL，显示出对氧化的敏感性增强，但是在体外与普伐他汀孵育对LDL氧化没有影响。（0.1 mg蛋白ml（-1）），对乙酰胆碱或A23187的内皮依赖性舒张功能受损，但从对照组或普伐他汀治疗组大鼠中分离的LDL没有这种作用。超氧化物歧化酶（SOD）是一种超氧化物清除剂，可阻止糖尿病LDL的这种抑制作用。5这些结果表明，普伐他汀可保护STZ诱导的糖尿病大鼠血管内皮功能，而不会降低血浆胆固醇，其作用可能是由于LDL氧化减少。
1 We investigated the effects of chronic pravastatin treatment on the impaired endothelium-dependent relaxation seen in aortae from established streptozotocin (STZ)-induced diabetic rats. Starting at 6 weeks of diabetes, pravastatin (10 mg kg(-1)) was administered to STZ-induced diabetic rats for 4 weeks.2 The increased total cholesterol and low-density lipoprotein (LDL) cholesterol levels seen in STZ-induced diabetic rats were not restored to normal by pravastatin. Aortae from pravastatin-treated diabetic rats did not show an impaired endothelium-dependent relaxation to acetylcholine. The expression of the mRNA for endothelial nitric oxide synthase was unaffected by diabetes or pravastatin.3 The enhanced level of malondialdehyde (MDA)-modified LDL seen in STZ-induced diabetic rats was normalized by pravastatin treatment. The resistance of LDL to oxidation was assessed by measuring the amount of MDA or conjugated dienes generated by incubation with copper ions. LDL isolated from diabetic rats, but not those from pravastatin-treated diabetics, showed enhanced the susceptibility to oxidation, but incubation in vitro with pravastatin had no effect on LDL oxidation.4 Following incubation of control aortae for 6 h with LDL (0.1 mg protein ml(-1)) isolated from diabetic rats, the endothelium-dependent relaxation to acetylcholine or A23187 was impaired, but LDL isolated from control or pravastatin-treated rats had no such effect. This inhibitory effect of diabetic LDL was prevented by superoxide dismutase (SOD), a superoxide scavenger.5 These results suggest that pravastatin preserves endothelial function in aortae from STZ-induced diabetic rats without lowering plasma cholesterol, and its effect may be due to decreased LDL oxidation.