血管紧张素(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

Treatment with angiotensin-(1-7)or captopril improves postischemic diastolic function recovery of the isolated hearts of diabetic rats

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/dt_(max))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/dt_(max))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。

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 rain of reperfusion. Leff 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.