糖尿病大鼠主动脉超微结构和功能变化及氯沙坦对其影响

摘要

目的探讨不同病程糖尿病大鼠主动脉超微结构和功能变化及血管紧张素Ⅱ受体(ART)拮抗剂氯沙坦对其影响。方法雄性SD大鼠随机分为正常对照组(NC)、糖尿病对照组(DC)、糖尿病治疗组(DL)。造模后第5 周起DL组每天予氯沙坦20mg/kg，于4、8、16周末测血糖、血浆内皮素(ET-1)和血管紧张素Ⅱ(Ang Ⅱ)，8、16周末取主动脉作电镜观察。结果 8 周时，DC组内皮细胞有线粒体肿胀，空泡变。16周时DC组病变加重并内皮细胞广泛坏死脱落，但DL组病变明显减轻。各病程中DC组血浆Ang Ⅱ均明显升高，ET-1在8周时明显升高，16 周时明显降低；16周时DL组与DC组比较Ang Ⅱ水平明显升高(P＜0.05)，ET-1则降低，但P＞0.05。结论糖尿病大鼠主动脉随病程不同而出现超微结构改变和功能异常，氯沙坦能明显改善这种病理变化，对糖尿病大鼠主动脉有一定保护作用。%Objective　To investigate the alteration in ultr astructure and function of the aorta in different times in diabetic rats and the effects of Losartan.Methods　Male SD rats were randomly d ivided into normal control group (NC)、diabetes control group (DC)、 diabetes gr oup treated with Losartan ［20mg/(kg*d)］which were administered a fter 5 weeks.At 4、8 and 16 weeks after injecting STZ,blood glucose,plasma endot helin-1 and angiotensin Ⅱ were measured respectively.Aortic endothelial cell w ere also observed under electron microscope at 8、16 weeks.Results　 In DC group,there were mitochondria edema and vacuolization in the ao rtic endothelial cells at 8 weeks,and extensive endothelial cell necrosis and ex foliation at 16 weeks,while pathological changes in DL group were abated signif icantly.Plasma Ang Ⅱ level were increased significantly in DC group,and plasma ET-1 level were obviously increased at 8 weeks and greatly decreased at 16 week s.In DL group,plasma AngⅡ level elevated significantly,while plasma ET-1 level declined (P＞0.05) compared with DC group at 16 weeks.Conclusion 　The ultrastructure and function undergo pathological changes with t he development of diabetes mellitus.Losartan can obviously improve pathological changes of the ultrastructure and function in diabetic rats and protect the aort a of diabetic rats.