肾素-血管紧张素系统在血管性痴呆大鼠心肌损伤中的作用

Role of the renin-angiotensin system in myocardial injury in rats with vascular dementia

目的探讨肾素-血管紧张素系统在实验性血管性痴呆大鼠心肌损伤中的作用。方法24只成年雄性SD大鼠分为正常组、假手术组和模型组。Morris水迷宫用于评估大鼠学习记忆功能;免疫染色法观察心肌细胞横截面积和间质胶原蛋白分数以评估实验性血管性痴呆引起的心肌改变。检测血清中血管紧张素Ⅱ(AngⅡ)和血管紧张素1-7(Ang1-7)的浓度,以及心肌中血管紧张素转换酶(ACE)、血管紧张素转换酶2(ACE2)、AngⅡ、Ang1-7、血管紧张素1型(AT1)受体和Mas受体的蛋白表达水平。结果与假手术组和正常组比较,模型组大鼠存在明显的认知功能障碍(P<0.01)和心肌损伤(P<0.0001)。此外,模型组大鼠心肌中肾素-血管紧张素系统的ACE/AngⅡ/AT1轴上调(P<0.01),而ACE2/Ang1-7/Mas轴下调(P<0.05)。结论实验性血管性痴呆大鼠心肌损伤可能与肾素-血管紧张素系统失调有关。

Objective To observe the role of the renin-angiotensin system in myocardial injury induced by experimental vascular dementia.Methods Eighteen adult male rats were categorized into a normal group,sham group,and modified 2-vessel occlusion group(model).To assess the myocardial injury caused by experimental vascular dementia,immunostaining was conducted to evaluate the interstitial collagen fraction and myocyte cross-sectional area.The concentrations of angiotensinⅡ(AngⅡ)and angiotensin 1-7(Ang1-7)in the serum,as well as the expression levels of angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2),AngⅡ,Ang1-7,angiotensin type 1(AT1)receptor,and Mas receptor in the myocardium,were assessed.Results Modified 2-vessel occlusion led to pronounced cognitive dysfunction(P<0.01)and myocardial injury(P<0.0001)when compared to the sham and normal groups.Additionally,modified 2-vessel occlusion induced significant upregulation of the ACE/AngⅡ/AT1 receptor axis(P<0.01)and downregulation of the ACE2/Ang1-7/Mas axis(P<0.05)of the renin-angiotensin system in the myocardium.Conclusion Myocardial injury in rats with experimental vascular dementia may be related to dysregulation of the renin-angiotensin system.