【摘要】 目的探讨氯沙坦对肾性高血压大鼠心肌组织中血管紧张素转换酶2(ACE2)和血管紧张素转换酶(ACE)表达的影响。方法将雄性SD大鼠60只随机分为假手术组(n=12)、高血压组(n=12)、高血压+氯沙坦(10mg/kg)组(n=12)、高血压+氯沙坦(20mg/kg)组(n=12)、高血压+氯沙坦(30mg/kg)组(n=12)。采用SD大鼠建立两肾一夹高血压大鼠模型,在手术后10周,给予氯沙坦治疗。给药4周后,心肌组织石蜡切片HE染色观察心肌形态学变化,Westernblot分析ACE及ACE2蛋白表达。结果3个剂量的氯沙坦明显降低高血压大鼠收缩压;高血压大鼠心肌细胞肥大、排列紊乱,氯沙坦治疗后心肌细胞肥大、排列紊乱程度降低。高血压大鼠心肌ACE2表达较假手术组降低[(0.49±0.01)比(0.88±0.03),P<0.01],ACE表达较假手术组大鼠升高[(1.21±0.07)比(0.61±0.02),P<0.01];氯沙坦剂量依赖性地增加大鼠ACE2表达,降低ACE表达,这种作用在20与30mg/kg两组与高血压组比较有显著差异(P<0.01)。心脏重构指数与ACE和ACE2比值存在显著相关(P<0.01)。结论氯沙坦能增加心肌组织ACE2表达,降低ACE表达可能是其降低血压和保护心脏的重要机制之一。更多还原

【Abstract】 Objective To investigate the effects of losartan on the expression of angiotensin-converting enzyme 2 (ACE2) and angiotensin-converting enzyme (ACE) in myocardium of hypertensive rats.Methods Sprague-Dawley male rats were underwent two kidney one clip(2K1C) operation and treated with losartan(10 mg/kg,n=12),(20 mg/kg,n=12),(30 mg/kg,n=12),for 4 weeks.Twelve SD rats received sham operation served as controls.Myocardial morphology was observed by HE staining;the expressions of ACE2 and ACE protein levels were detected with Western blot assay.Results Compared with sham group,the expression of myocardial ACE2 was decreased significantly [(0.49±0.01) vs (0.88±0.03),P<0.01],and the expression of ACE was increased obviously[(1.21±0.07) vs (0.61±0.02),P<0.01] with concomitant increases in SBP.All three doses of losartan decreased the blood pressure and LVM/weight ratio in hypertensive rats significantly (P<0.05).Losartan increased ACE2 and decrease of ACE expressions in dose-dependent manner.The myocardial remodeling index (heart weight/body weight) was closely related to the ACE/ACE2 ratio(P<0.01).Conclusion The reversing of ACE2 and ACE expression in myocardial tissue may be one of the mechanisms governing losartan antihypertensive and myocardial protection effect in the 2K1C hypertensive rats.更多还原