·糖尿病基础研究·

　　赵 竞、王方岩、汪 洋、许益笑、金可可

　　作者单位：325035，温州医学院病理生理教研室

　　【摘要】目的  观察血管紧张素(1-7)[AT-(1-7)]和卡托普利预处理对糖尿病大鼠心功能的影响并探讨其可能机制。方法  SD大鼠分为糖尿病对照(DM)组、糖尿病AT-(1-7)处理(DM+AT)组、糖尿病卡托普利处理(DM+Cap)组。采用Langendorff离体心脏灌流系统检测心功能，心肌缺血20 min再灌注20 min后，检测心功能指标、心肌氧化应激水平、胶原总量、胶原交联及赖氨酰氧化酶(LOX)的表达水平。结果   缺血再灌注后，DM组各心功能指标较基线明显下降，DM+AT组和DM+Cap组的左心室收缩末压(LVESP)和左心室压力上升最大变化速率(+dp/dtmax)较基线明显下降(P<0.01)，但左心室压力下降最大变化速率(-dp/dtmax)未见明显降低(P>0.05)。与DM组比较，DM+AT组和DM+Cap组丙二醛(MDA)含量显著降低，超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力显著增高。DM+AT组和DM+Cap组心肌胶原交联百分率和LOX蛋白表达低于DM组。结论  AT-(1-7)和卡托普利预处理促进糖尿病大鼠离体心脏缺血后舒张功能的恢复，其机制可能与增强糖尿病大鼠心肌的抗氧化能力、抑制胶原交联、LOX降低有关。

　　【关键词】血管紧张素(1-7);血管紧张素转换酶抑制剂;糖尿病;心脏;胶原

　　doi:10.3969/j.issn.1006-6187.2011.12.016

　　Treatment with angiotensin-(1-7) or captopril improves postischemic diastolic function recovery of the isolated hearts of diabetic ratsZHAO Jing, WANG Fang-yan, WANG Yang, et al. Department of Pathophysiology of Wenzhou Medical College, Wenzhou 325035, China

　　【Abstract】Objective  To explore the effects of angiotensin (AT)-(1-7) or captopril on isolated cardiac function of diabetic rats. Methods  SD rats were divided into 3 groups: diabetic control group(DM), diabetic rats treated with AT-(1-7) group (DM+AT) and diabetic rats treated with captopril group (DM+Cap). Animals were killed at four weeks after induction of diabetes and/or treatment with AT-(1-7) or captopril. The isolated Langendorff-perfused rat hearts were subjected to ischemia for 20 min followed by 20 min of reperfusion. Left ventricular function, myocardial markers of oxidative stress, collagen concentration, cross-linked collagen and lysyl oxidase (LOX) were examined. Results  Treatment with AT-(1-7) or captopril significantly improved postischemic left ventricular -dp/dtmax. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased, and the levels of malondialdehyde (MDA), cross-linked collagen and LOX were significantly decreased in the myocardium of (DM+AT) and (DM+Cap) rats as compared with control rats. Conclusion  Treatment with AT-(1-7) or captopril improves postischemic diastolic function recovery in diabetic hearts.The mechanism might be related to the upregulation of antioxidant enzymes, the reduction of cross-linked collagen and the expression of LOX.

　　【Key words】 AT-(1-7);Angiotensin-converting enzyme inhibitor;Diabetes;Heart;Collagen