血管紧张素受体阻滞剂对自发性高血压大鼠肾脏血管紧张素转换酶2表达的影响

Effects of angiotensin type-1 receptor blockade on expression of angiotensin-converting enzyme 2 in renal of spontaneously hypertensive rats

目的:研究自发性高血压大鼠肾脏血管紧张素转换酶2(ACE2)蛋白表达水平及血管紧张素ⅡⅠ型受体阻滞剂厄贝沙坦对ACE2表达的影响,以了解高血压的病理改变,探讨血管紧张素受体阻滞剂治疗高血压又一可能机制。方法:20只14周龄雄性自发性高血压大鼠随机分为自发性高血压大鼠(SHR)组(n=10)和厄贝沙坦组(n=10)。厄贝沙坦组每只大鼠以厄贝沙坦50mg·kg-1·d-1灌胃,给药时间12周。同时取14周龄雄性京都种Wistar大鼠为正常对照(WKY)组(n=10)。利用免疫组化和逆转录聚合酶链反应检测各组大鼠肾脏ACE2表达。结果:与WKY组比较,SHR组ACE2表达显著减少(0.72±0.11vs1.11±0.15);与SHR组比较,厄贝沙坦组经12周治疗后,ACE2表达明显提高(1.03±0.13vs0.72±0.11)。结论:高血压大鼠肾脏ACE2表达减少,血管紧张素ⅡⅠ型受体阻滞剂对高血压大鼠肾脏ACE2的表达有上调作用。此作用可能是血管紧张素受体阻滞除阻滞血管紧张素受体以外的另一间接调节肾素-血管紧张素系统的途径。

AIM: To investigate the expression of angiotensin-converting enzyme 2 (ACE_2) in the renal of spontaneously hypertensive rats and the effects of angiotensin type-1 receptor blockade. METHODS: Twenty of 14-week-old male SHR were randomly divided into two groups (n=10 in each): SHR group and irbesartan group. Ten of 14-week-old male WKY group were served as control. Irbesartan group were given a daily dose of 50 mg·kg -1 irbesartan for 12 weeks by gavage and the other two groups were fed with a normal diet. Angiotensin-converting enzyme 2 was examined by immunohistochemistry and RT-PCR. RESULTS: ACE_2 in the renal was significantly down-regulated in the SHR group compared with the WKY group ( 0.72± 0.11 vs 1.11± 0.15). After 12 weeks treatment with irbesartan, the attenuated ACE_2 expression in irbesartan group was markedly enhanced compared with the SHR group ( 1.03± 0.13 vs 0.72± 0.11). CONCLUSION: Hypertension induces the reduction of ACE_2 in the renal in rats and irbesartan markedly increases ACE_2 expression. It suggests that up-regulation ACE_2 which is one of counter-regulatory particular components in the renin-angiotensin system may be a new mechanism of curing hypertension beyond blockade angiotensin type-1 receptor.