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目的观察自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)的表达,探讨伊贝沙坦对SHR肾脏ACE2 mRNA表达的调节作用。方法20只14周龄雄性SHR分为SHR组和伊贝沙坦组,各10只。伊贝沙坦组每只大鼠予以伊贝沙坦50 mg·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10只为对照组。SHR组和对照组给予等量蒸馏水灌胃12周。采用免疫组织化学和逆转录聚合酶链反应检测各组大鼠肾脏ACE2表达,利用放射免疫测定法检测各组大鼠血浆血管紧张素(Ang)Ⅱ浓度。结果与对照组比较,SHR组ACE2 mRNA表达显著减少(0．72±0．11对1．11±0．15);与SHR组比较,伊贝沙坦组经12周治疗后,ACE2 mRNA表达明显提高(1．03±0．13对0．72±0．11),均为P<0．05。SHR肾脏ACE2 mRNA表达与血浆AngⅡ浓度成正相关(r=0．83,P<0．05)。结论ACE2在高血压大鼠肾脏表达显著减少,可能是高血压病理生理变化之一。AngⅡ-1型受体阻滞剂伊贝沙坦上调SHR肾组织ACE2 mRNA表达,提示这可能是该药物反向调节过度激活的肾素-血管紧张素系统又一新途径。
Objective To investigate the expression of angiotensin converting enzyme 2 (ACE2) in spontaneously hypertensive rats (SHR) and to explore the regulatory effect of irbesartan on the expression of ACE2 mRNA in SHR kidney. Methods Twenty male SHRs of 14 weeks old were divided into SHR group and irbesartan group, 10 in each. Each group in irbesartan group was treated with irbesartan 50 mg · kg -1 · d -1 intragastrically for 12 weeks. Meanwhile, 10 male Wistar rats of 14 weeks old were used as the control group. SHR group and control group were given equal volume of distilled water for 12 weeks. Immunohistochemistry and reverse transcription polymerase chain reaction were used to detect the expression of ACE2 in kidney of rats in each group. Plasma Angiotensin (Ang Ⅱ) concentration was measured by radioimmunoassay. Results Compared with the control group, the expression of ACE2 mRNA in SHR group was significantly decreased (0.72 ± 0.11 vs 1.11 ± 0.15). Compared with SHR group, the expression of ACE2 mRNA in irbesartan group after 12 weeks of treatment (1.03 ± 0.13 vs. 0.72 ± 0.11), both P <0.05. The expression of ACE2 mRNA in SHR kidney was positively correlated with plasma AngⅡ concentration (r = 0.83, P <0.05). Conclusion The expression of ACE2 is significantly reduced in the kidney of hypertensive rats, which may be one of the pathophysiological changes of hypertension. Irbesartan, an angiotensin II-1 receptor blocker, up-regulates ACE2 mRNA expression in SHR, suggesting that this may be another new way for the drug to inversely regulate the over-activated renin-angiotensin system.