摘要
目的观察缬沙坦、苯那普利及缬沙坦和苯那普利联用对慢性肾衰竭大鼠心肌病变的改善作用,探讨其作用机制。方法SD♂大鼠40只,通过5/6肾切除法制备慢性肾衰竭模型,术后2wk随机分为模型组、缬沙坦组、苯那普利组及缬沙坦与苯那普利联合治疗组,并设假手术组作为对照。术后第10周末测定各组大鼠血压及肾功能(Scr、BUN)后处死大鼠,取出心脏进行病理组织学观察;并采用原位杂交方法检测心肌内皮素-1(ET-1)mRNA及一氧化氮合酶3(eNOS-3)mRNA的转录水平。结果模型组术后第10周收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数均明显增加,缬沙坦、苯那普利及联合治疗组能明显降低5/6肾切除大鼠收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数(P<0.01);缬沙坦组、苯那普利组及联合治疗组心肌ET-1mRNA、eNOS-3 mRNA转录水平均较模型组减弱。结论缬沙坦、苯那普利及缬沙坦与苯那普利联合治疗能防治慢性肾衰竭大鼠的左室肥厚,其机制可能是通过下调心肌ET-1 mRNA、eNOS-3 mRNA转录来实现的。
Aim To observe the protective effect of valsartan , benazepril and combination valsartan with benazepril on cardiac damage in rats with chronic renal failure and explore the mechanism. Methods Forty Sprague Dawley male rats were selected, and were performed five-sixths nephrectomy to produce chronic renal failure model. Two weeks after the surgery, the rats were divided randomly into model group, valsartan group, benazepril group and both valsartan and benaze- pril group, and a sham group was established as control group. Systolic blood pressure, BUN and serum creatinine was measured at 10 week after operation, then all rats were killed to take the hearts for pathological histological observation. The transcription of endothelin-1 （ET-1） mRNA and nitricoxide synthase （eNOS-3） mRNA in myocardium was examined by hybridization in situ. Results Systolic pressure, heart weight, heart weight index, left ventricular weight mass （LVWM） and left ventricular weight mass index （LVWMI） in model group increased significantly at 10 week after operation. Systolic pressure, heart weight, heart weight index, LVWM and LVWMI decreased markedly in rats with five-sixths nephrectomy by valsartan and/or benazepril （P 〈 0. 01 ）. Hybridization in situ indicated that there was an decreasing expression of ET-1mRNA and eNOS-3 mRNA in myocardium in three treatment groups compared with model group. Conclusion Valsartan and benazepril could prevent cardiac damage in chronic experiment renal failure rats. The improvement of cardiomyopathy may be through the mechanism of downregulating transcription of ET-lmRNA and eNOS- 3mRNA in myocardium.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2008年第12期1599-1603,共5页
Chinese Pharmacological Bulletin
基金
安徽省学术技术带头人后备人选项目
安徽省教育厅科学研究基金资助项目(No2002HBL25
2003KJ319)
关键词
血管紧张素转化酶抑制剂
血管紧张素Ⅱ受体拮抗
剂
慢性肾衰竭
左室肥厚
内皮素
一氧化氮合酶
转录
angiotensin converting enzyme inhibitor
angiotensin Ⅱ receptor antagonist
chronic renal failure
left ventricular hypertrophy
endothelin-1
nitricoxide synthase
transcription
