自发性高血压大鼠高血压进程中心肌血管紧张素转换酶的变化及卡托普利干预作用

Changes of angiotensin-converting enzyme and intervention of captopril in processing of hypertension in spontaneously hypertensive rats

目的探讨自发性高血压大鼠(SHR)肥厚心肌中血管紧张素转换酶(ACE)和ACE2的改变及卡托普利的作用。方法 7周龄SHR大鼠,ig给予卡托普利3.375 g·kg-1,每天1次,连续17周,至24周龄。分别于18,24和32周龄测血压、左心室质量指数(LVMI);实时PCR法检测ACE mRNA和ACE2mRNA的表达,ELISA法检测ACE和ACE2蛋白的表达。结果从18到32周龄,SHR模型组和正常Wistar-Kyoto(WKY)大鼠组的血压和LVMI基本无变化。与同龄WKY大鼠相比,SHR血压和LVMI均显著升高(P<0.01)。给予卡托普利3.375 g·kg-1,可显著降低血压(18和24周龄)和LVMI(24周龄)(P<0.05),停药后作用消失。与18周龄的SHR相比,32周龄的SHR心肌ACE mRNA与ACE2 mRNA及蛋白比值显著升高(P<0.01)。与同龄WKY大鼠相比,24和32周龄的SHR ACE mRNA与ACE2mRNA比值显著升高(P<0.01);18,24和32周龄时,其蛋白比值显著升高(P<0.01)。SHR给予卡托普利,18,24和32周龄时心肌ACE mRNA与ACE2 mRNA及蛋白比值均显著降低(P<0.05),其mRNA比值由5.42±0.82,37.44±6.76和71.73±4.30分别降低到1.45±0.09,15.40±2.62和6.82±2.84,其蛋白比值由4.61±0.29,5.76±0.93和6.13±0.23分别降低到2.94±0.23,3.02±0.07和2.79±0.10。结论 SHR肥厚心肌中ACE和ACE2表达失衡,卡托普利通过激活ACE2 mRNA及蛋白表达而调节ACE与ACE2的比值,说明其可能通过改善ACE与ACE2的比值从而减轻高血压及其左心室肥厚。

OBJECTIVE To investigate the effect of captopril to the changing the angiotensin-converting enzyme （ACE） and ACE2 in renin-angiotensin system on the progressing of left ventricular hypertrophy in spontaneously hypertensive rats （SHRs）. METHODS Seven-week-aged SHRs were administered captopril 3.375 g·kg-1, once daily, for 17 weeks （24-week-aged stage）. Blood pressure （BP） and the left ventricular mass index （LVMI） were measured on the 18-, 24-and 32-week-aged stage. The mRNA expressions of ACE and ACE2 in heart tissue were measured by Real time PCR and proteins were measured by ELISA. RESULTS From 18-to 32-week of age, BP and LVMI in SHRs and Wistar-Kyoto （WKY） rats had no change. BP and LVMI in SHRs were higher than that in WKY rats in each corresponding time point （P〈0.01）. After SHRs were administered captopril 3.375 g·kg-1, BP significantly decreased （on the 18-and 24-week-aged stage） and LVMI significantly decreased （on the 24-week-aged stage） （P〈0.05）. However, this effect disappeared after ceasing dose. Compared with 18-week-aged SHRs, the ratios of mRNA or protein of ACE to ACE2 in 32-week-aged SHRs significantly increased （P〈0.01）. The ratios of ACE mRNA and ACE2 mRNA were higher than that in WKY rats at 24-and 32-week of age （P〈0.01）. The ratios of ACE and ACE2 protein in SHRs were higher than that in WKY rats in each corresponding time point （P〈0.01）. When SHRs were administered captopril, the ratios of mRNA or protein of ACE to ACE2 decreased （P〈0.05）, the ratios of ACE mRNA to ACE2 mRNA at 18-, 24-and 32-week of age decreased from 5.42±0.82, 37.44±6.76 and 71.73±4.30 to 1.45±0.09, 15.40±2.62 and 6.82±2.84. The ratios of ACE to ACE2 protein at 18, 24 and 32 weeks of age were decreased from 4.61±0.29, 5.76±0.93 and 6.13±0.23 in SHR to 2.94±0.23, 3.02±0.07 and 2.79±0.10. CONCLUSION The expressions of ACE and ACE2 in hypertrophic cardiac myocyte of SHRs are unbalanced. Captopril adjusts the ratios of ACE and ACE2 by activating ACE2 mRNA and protein expressions, which suggests its possible that reducing hypertension and left ventricular hypertrophy via improving the ratios of ACE and ACE2.