苯那普利、缬沙坦对糖尿病大鼠肾脏血管紧张素转换酶2表达的影响

The Effects of Benazepril and Valsartan on the Expression of Angiotensin Converting Enzyme2 in Kidney of Diabetic Rats

目的观察糖尿病大鼠肾脏血管紧张素转换酶2(ACE2)的表达及苯那普利、缬沙坦对糖尿病大鼠肾脏ACE2表达水平的影响,初步探讨ACE2在糖尿病肾病发病机制中的作用。方法3月龄的SD雄性大鼠,腹腔内注射链脲佐菌素建立糖尿病大鼠模型,随机分为3组,每组7只,分别为糖尿病模型组、苯那普利治疗组[10mg/(kg.d)]、缬沙坦治疗组[10mg/(kg.d)],SD雄鼠7只作为正常对照组。给药3月后,处死动物、留取标本,反转录-聚合酶链式反应(RT-PCR)法测定肾脏中ACE和ACE2 mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达水平。结果与正常对照组相比,糖尿病模型组大鼠ACE、ACE2 mRNA表达分别下降30.7%、50.1%(P<0.05)。与糖尿病模型组比较,苯那普利组ACE mRNA的表达明显增加(P<0.01),ACE2 mRNA的表达无明显差异;缬沙坦组ACE mRNA的表达治疗后没有明显变化,而ACE2 mRNA和蛋白的表达均有明显增加,分别增加68.7%和69.8%(P<0.01)。结论1)肾脏局部ACE2表达水平的降低可能是糖尿病大鼠肾损害的发病机制之一;2)ARB可能是通过增加肾脏局部ACE2的表达而发挥肾脏保护作用。

Objective To investigate the expression of angiotensin converting enzyme2 （ACE2） in the kidney of diabetic rats and the effects of benazepril and valsartan on ACE2 expression and the role of ACE2 in the pathogenesis of diabetes. Methods Experimental diabetes was established in 12 week-old male Spraque Dawley rats by intraperitoneal injection of the streptozocin. The rats were randomed into three groups： diabetic control （n=7）, benazeprill[n=7, 10 mg/（kg · d）], valsartanl[n= 7,10 mg/（kg · d）], 7 normal male SD rats were served as placebo control. ACE and ACE2 mRNA in kidney was determined by RT-PCR and ACE2 protein was measured by immunohistochemistry after 3 months administration. Results The expression of ACE and ACE2 mRNA in diabetic kidney was lower than that in the placebo control by 30.7% and 50. 1 % （P〈0.01）. Benazepril significantly increased the expression of ACE mRNA （P〈0. 01） while no change in ACE2 mRNA expression was found. On the contrary, valsartan treatment increased the expression of ACE2 （mRNA and protein） by 68. 70% and 69.8% （P〈0. 01） but no change in ACE mRNA expression was found. Conclusion 1 ）Diabetic nephropathy was associated with decreases of ACE2 expression in kidney. 2）The renoprotection effect of angiotensin receptor blocker （ARB） may be ascribed to the increased ACE2 in kidney.