摘要
目的评估辛伐他汀对于胆固醇喂养兔的血管内皮影响。方法１４只新西兰大白兔喂以高胆固醇饲料（１％胆固醇）１０周，在４周后随机分成两组，一组（Ｂ组）继续给高胆固醇饲料，一组（Ｃ组）为高胆固醇饲料加辛伐他汀（２ｍｇ·ｋｇ１·ｄ１）。第三组（７只，Ａ组）给予标准饲料，１０周后取血测血脂包括总胆固醇，低、高密度脂蛋白胆固醇及甘油三酯。麻醉后分离胸主动脉去除结缔组织及脂肪组织，取近主动脉弓处一小段置固定液（２％ｇｌｕｔａｒａｌｄｅｈｙｄｅ）中送电镜检查，其余切成４ｍｍ长的血管环置浴槽中做离体实验，观察对乙酰胆碱、去甲肾上腺素、５羟色胺及硝酸甘油的剂量反应曲线。结果Ｂ组血管对乙酰胆碱的内皮依赖性舒张功能明显减弱；且对于去甲肾上腺素和５羟色胺的收缩功能增强。而Ｃ组这些功能接近正常组（Ａ组），三组血管对非内皮依赖性舒张剂硝酸甘油的反应相似。Ｂ组血胆固醇水平升高，而Ｃ组此值明显下降。三组的高密度脂蛋白胆固醇水平未见明显差异。电镜观察发现Ｂ组主动脉内膜和临近的中膜有明显脂质沉积，而Ｃ组此病变明显改善。结论辛伐他汀可预防服高胆固醇饲料兔的血管内皮功能紊乱。这种对动脉内皮的保护作用与其降低血胆固醇水平和血管壁的形态学变化有关?
Objective Endothelium dependent relaxation in arteries is attenuated in clinical and experimental atherosclerosis. The present study was designed to observe whether oral simvastatin would protect endothelium dysfunction in atherosclerotic aorta in rabbit induced by cholesterol diet. Methods Twenty one male New Zealand white rabbits were randomly divided into three groups. Group A were fed a standard diet, group B and group C were fed contained 1% cholesterol diet for 10 weeks and group C received simutaniously simvastatin 2mg/kg/day for the last 6 weeks. At the beginning and end of the dietary intervention, the rabbit blood samples were collected for measurement of the lipid profile. The rabbits were killed after the dietary intervention, the thoracic aorta was isolated and segments adjacent to aortic arch were harvested for electron microscopy review, while the others were cut into 4 mm rings and mounted in organ bath for measurement of isometric force development. Dose reponse curves to acetylcholine, noradrenaline, serotonin and nitroglycerine were constructed. Results Endothelium dependent relaxation to acetylcholine was significantly impaired in aortic rings in group B, but there was no significantly difference in group A and group C for responses to acetylcholine. Responsiveness to the endothelium independent vasodilator, nitroglycerine, was similar in arteries from 3 groups. The contractive responses to noradrenaline and serotonin were increased in group B. However, these responses of group C were similar to group A. Total cholesterol levels were elevated in the rabbits that were fed cholesterol diet and decreased in cholesterol fed supplemented with simvastatin. High density lipoprotein cholesterol levels were no different in three groups. The electron microscopy observation revealed that lipid deposition in the intima and subjacent media was marked in group B, but simvastatin improved these changes in group C. Conclusion Simvastatin prevents endothelial dysfunction in cholesterol fed rabbits. This improvement appears to be related to the decrease of serum cholesterol levels and morphologic changes.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
1998年第5期379-382,共4页
Chinese Journal of Cardiology
关键词
辛伐他汀
动脉粥样硬化
药物疗法
simvastatin atherosclerosis endothelium, vascular
