【摘要】 目的　探讨糖尿病性心肌病的发生、发展并试用氯沙坦干预治疗 ,为糖尿病性心肌病的防治提供参考。方法　建立 3个月、6个月糖尿病大鼠模型 (糖尿病组 ) ,放射免疫法测定糖尿病组血浆及心肌局部血管紧张素Ⅱ (AngⅡ )、测定心脏重量指数、dp/dtmax比值并作心肌形态学观察 ,与对照组、氯沙坦干预组相比较。结果　糖尿病组心肌局部AngⅡ 6个月明显增高 ,血浆AngⅡ 3个月、6个月持续增高 ;心脏重量指数 3个月、6个月持续高于对照组 ;心脏 dp/dtmax3个月、6个月进行性下降 ,差异具有显著性 ;糖尿病组心肌细胞线粒体肿胀、空泡样变 ,肌原纤维排列紊乱 ,细胞间质胶原增生 ,心肌微血管基膜增厚。氯沙坦干预组心肌局部和血浆AngⅡ变化不明显 ,心脏重量指数明显下降 ,血压明显下降 ;+dp/dtmax、-dp/dtmax均有所上升 ,微血管基膜增厚减轻 ,间质胶原减少 ,心肌细胞超微结构改变不明显。结论　AngⅡ在糖尿病性心肌病模型的发生中起重要作用 ,发病早期应用氯沙坦在一定程度上可阻抑糖尿病性心肌病发展进程。更多还原

【Abstract】 Objective To investigate the development of diabetic cardiomyopathy, the angiotensin Ⅱ AT-1 receptor antagonist, losartan, was used to the diabetic rats in order to provide the evidence of the prevention and treatment of diabetic cardiomyopathy. Methods Wistar rats were divided into two groups, namely, 3-month group: diabetes ( n = 8, rats were administrated by streptozotocin 60 mg·kg -1 intraperitoneally) and controls ( n = 8); 6-month group: diabetes ( n =10), losartan treated diabetes (oral dose=3 mg·kg -1 ·d -1 , duration of treatment from 3 to 6 months after diabetes induced, n =10) and controls ( n =10). The plasma and tissue AngⅡ and some related parameters were determined at 3rd and 6th month. Results The myocardial AngⅡ was significantly higher in 6-month diabetes than that in control [(753 4±52 03) pg/g vs (544 1±58 24) pg/g, P < 0 01]; plasma AngⅡ (976 5±131 16) pg/ml, was increased significantly in 3-month diabetes as compared with the control (416 9±75 56) pg/ml, P <0 01, and it lasted to 6-month (885 4±103 10) pg/ml vs (399 9± 62 93) pg/ml. The cardiac mass index was apparently higher in 3-and 6-month diabetes than that in the correspondent controls,-dp/dt max was decreased in 3-and 6-month diabetes as compared with controls [(687± 85 9) mm Hg/s vs (864±94 3) mm Hg/s, (632±63 9) mm Hg/s vs (844±64 6) mm Hg/s, P <0 05, respectively] and had a downward trend. +dp/dt max decreased markedly in 6-month diabetes. Within cardio- cytes., diabetes produced a focal loss and disorganization of myofibril, mitochondria swelling, and lysis of cistae. The separation of the fasciae adherens was evident at the intercalated disk, and irregular thickening of basal laminar changes were also found. In losartan treated group, the tissue and plasma AngⅡ did not show any apparent change, the cardiac mass index and blood pressure were decreased significantly, both +dp/dt max and -dp/ dt max were increased markedly as compared with diabetes. Proliferations of the collagen in the extracellular matrix and basal laminae alteration were partially reversed by losartan treatment. Conclusion These findings indicated that AngⅡ may play a role in the pathogenesis of diabetic cardiomyopathy, the administration of angiotensin Ⅱ receptor antagonist, losartan, could partially reverse the change of diabetic heart.更多还原