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。
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.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2010年第1期71-74,共4页
Chinese Journal of Hypertension
基金
湖南省郴州市科技计划项目(06CK50)
关键词
血管紧张素转换酶
心脏重构
氯沙坦
肾性高血压大鼠
Angiotensin-converting enzyme
Myocardial remodeling
Losartan
Renal hypertensive rat
