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

Changes in ultrastructure and function of the aorta in diabetic rats and the effects of Losartan

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 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 2 0 mg/ kg,于 4、8、16周末测血糖、血浆内皮素 (ET- 1)和血管紧张素 (Ang ) ,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 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 水平明显升高 (P<0 .0 5 ) ,ET- 1则降低 ,但 P>0 .0 5。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 。

Objective To investigate the alteration in ultrastructure and function of the aorta in different times in diabetic rats and the effects of Losartan.Methods Male SD rats were randomly divided into normal control group (NC)、diabetes control group (DC)、 diabetes group treated with Losartan [20mg/(kg·d)]which were administered after 5 weeks.At 4、8 and 16 weeks after injecting STZ,blood glucose,plasma endothelin-1 and angiotensin Ⅱ were measured respectively.Aortic endothelial cell were also observed under electron microscope at 8、16 weeks.Results In DC group,there were mitochondria edema and vacuolization in the aortic endothelial cells at 8 weeks,and extensive endothelial cell necrosis and exfoliation at 16 weeks,while pathological changes in DL group were abated significantly.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 weeks.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 the development of diabetes mellitus.Losartan can obviously improve pathological changes of the ultrastructure and function in diabetic rats and protect the aorta of diabetic rats.