论文部分内容阅读
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 renal hypertensive rats. Methods Sixty male Sprague-Dawley rats were randomly divided into sham operation group (n = 12), hypertension group (n = 12), hypertension group and losartan 10 mg / kg group (n = 12) Losartan (20 mg / kg) group (n = 12) and hypertension plus losartan (30 mg / kg) group (n = 12). SD rats were used to establish two-kidney-one-clip hypertensive rat models, and losartan was given 10 weeks after the operation. After 4 weeks of administration, the myocardial histological changes of paraffin sections were observed by HE staining, and the expressions of ACE and ACE2 were analyzed by Western blot. Results Three dosages of Losartan significantly reduced systolic blood pressure in hypertensive rats. Hypertensive rats showed hypertrophy and disorganized cardiomyocytes. Cardiomyocytes hypertrophy and disorder were reduced after losartan treatment. The expression of ACE2 in hypertensive rats was significantly lower than that in sham operated rats [(0.49 ± 0.01) vs (0.88 ± 0.03), P <0.01], and the ACE expression was significantly higher than that in sham operated rats [(1.21 ± 0.07) vs 0.02), P <0.01]. Losartan increased the ACE2 expression in a dose-dependent manner and decreased the expression of ACE. The effect of losartan on the levels of ACE2 and ACE2 was significantly different between the 20 and 30 mg / kg groups (P <0.01). There was a significant correlation between cardiac remodeling index and ACE and ACE2 (P <0.01). Conclusion Losartan can increase the expression of ACE2 in myocardium and decrease the expression of ACE may be one of its important mechanisms of lowering blood pressure and protecting the heart.