依那普利对自发性高血压大鼠心肌ACE和ACE2表达的影响

Effects of enalapril on the expression of cardiac angiotensin-converting enzyme andangiotensin-converting enzyme 2 in spontaneously hypertensive rats

目的观察自发性高血压大鼠(SHR)心肌的血管紧张素转换酶(ACE)和ACE2的表达,以及依那普利干预的影响。方法将15只SHR随机分为:SHR对照组(n=7)和依那普利组(n=8),分别给予安慰剂、依那普利15 mg/(kg.d)灌胃干预4周。干预结束后处死大鼠,分离左心室,行RT-PCR、Western blot检测。同步取10只WKY大鼠作为正常血压对照组。结果 SHR心肌ACE的mRNA和蛋白质的表达都显著高于WKY组(1.68±0.34 vs 0.33±0.12和1.21±0.14 vs 0.71±0.11,P<0.05),而ACE2的mRNA和蛋白质表达皆明显低于WKY组(0.50±0.15 vs1.16±0.24和0.71±0.24 vs 1.22±0.14,P<0.05)。依那普利明显降低ACE的mRNA和蛋白质表达(0.44±0.19 vs1.68±0.34,P<0.01;0.87±0.13 vs 1.21±0.14,P<0.05),提升ACE2的mRNA表达(1.77±0.49 vs 0.50±0.15,P<0.05),对ACE2的蛋白表达无明显影响。结论 SHR心肌ACE明显升高,ACE2显著降低;依那普利可能通过降低ACE、升高ACE2而降低血压。

Objective To investigate the cardiac expression of angiotensin-converting enzyme （ACE） and ACE2 in spontaneously hypertensive rats （SHR） and the effects of enalapril on them. Methods Fifteen SHR were randomly assigned to two groups： SHR control group （n = 7）which were treated with vehicle and enalapril group （n = 8 ）which were treated with enalapril [ 15 mg/（kg ·d）]. The treatment lasted for 4 weeks. After the treatment, the rats were killed and the left ventricular tissue was dissected carefully. Reverse transcription polymerase chain reaction （RT- PCR） and Western blot protein staining were performed to detect the expression of mRNA and protein of ACE and ACE2 respectivlely. Ten WKY rats surved as the normotensive control group which were also treated with vehicle. Re- suits In SHR, compared with the normotensive WKY, the cardiac expression of both mRNA and protein of ACE in SHR was obviously increased（ 1.68±0. 34 vs 0. 33 ±0. 12 and 1.21 ±0. 14 vs O. 71 ±0. 11, P 〈0. 05）, whereas the cardiac levels of both mRNA and protein of ACE2 were significantly decreaed（0. 50 ±0. 15 vs 1.16 ±0. 24 and 0. 71± 0. 24 vs 1.22 ±0. 14, P 〈 0. 05）. After treatment with enalapril, the expression of both ACE mRNA and ACE protein was obviously decreased（0. 44 ±0. 19 vs 1.68 ±0. 34, P 〈0. 01 ; 0. 87 ±0. 13 vs 1.21 ±0. 14, P 〈0. 05） and the expression of ACE2 mRNA significantly elevated （ 1.77 ±0. 49 vs 0. 50 ±0. 15, P 〈 0. 05 ）, but ACE2 protein re- mained unchanged. Conclusions In SHR, the expression of cardiac ACE remarkably increased, whereas ACE2 nota- bly decreased. Reduction of ACE and elevation of ACE2 is one of the potertial mechanisms underlying the antihypertensive function of enalapril.