依那普利和缬沙坦对自发性高血压大鼠心肌细胞凋亡的影响

Effects of enalapril and valsartan on myocardial apoptosis in spon-taneous hypertensive rat

目的观察依那普利和缬沙坦在降压的同时对自发性高血压大鼠(SHR)左室肥厚过程中心肌细胞凋亡及凋亡相关蛋白bc l-2、bax表达的影响。方法14周龄雄性SHR随机分为三组(n=6),依那普利组:依那普利30 mg.kg-1.d-1;缬沙坦组:缬沙坦30 mg.kg-1.d-1;对照组:等量饮用水灌胃,干预8周。分别采用流式细胞术Annexin V/PI法和免疫组化SABC法检测心肌细胞凋亡指数及凋亡相关蛋白bc l-2、bax的表达。结果缬沙坦及依那普利治疗组大鼠血压及左室重量/体重明显降低,心肌细胞凋亡指数明显降低(P<0.01);依那普利组明显降低bax蛋白表达,增加bc l-2蛋白表达(P<0.01)。缬沙坦组明显降低bax蛋白表达(P<0.01)。结论依那普利和缬沙坦对SHR左室肥厚过程中心肌细胞凋亡均有抑制作用。两者均通过增加bc l-2/bax比率而抑制心肌细胞凋亡,逆转高血压引起的左室肥厚。

Objective To observe the effrcts of enalapril and valsartan on myocardial apoptosis and the expression of proteins bcl-2/bax in the left ventricle of SHR when the blood pressure was reduced. Methods Eighteen male SHRs were divided into three groups （ n = 6, each group） ,which were treated with enalapril,valsartan （ 30 mg·kg·d^-1） or placebo for 8 weeks. The apoptosis index of cardiomyocytes and expression of protein bcl-2 and bax were detected by using Annexin V/PI and SABC immunohistoehemistry. Results Blood pressure of the three groups at 22 week were enalapril（ 126. 0 ± 2.9 ）mm Hg, valsartan（ 131.7 ±3. 1 ）mm Hg, placebo（ 218.0 ±4. 1 ）mm Hg respectively. The LV/BW ratio was lower：enalapril（ 2.72 ± 0. 05 ） mg/g; valsartan（ 2. 74±0. 04 ）mg/g and placebo（ 3.45±0. 06）mg/g. The index of apoptosis in enalapril and valsartan were（ 3.98 ± 0. 62） % and （4. 06± 0.44 ） % which was significantly less than that of placebo （ 8.64± 0. 58） %. The expression of bax in placebo group was markedly higher than that in enalapril and valsartan group. The ratio of bel-2/bax in placebo was obviously lower than that of enalaril and valsartan. Conclusions Both enalapfil and valsartan can inhabit myocardial apoptosis through increasing Bel-2/bax to reverse left ventricle hypertrophy in SHR.