依那普利、络沙坦合用对自发性高血压病鼠心肌细胞凋亡影响的研究

目的 观察血管紧张素转换酶抑制剂（ACEI）、血管紧张素Ⅱ受体I拮抗剂（ABB）单用及合用在治疗自发性高血压病鼠（SHR）过程中，左室重构及心肌细胞凋亡的差异，探究两类药物合用的机理。方法 依那普利（Enalapril)、氯沙坦（Losartan)单用及两药合用（剂量为单用时的半量）等三种方法冶疗18月龄的SHR16月后，测量左心室的天小，心肌细胞的凋亡指数以及bcl-2,Fas蛋白的表达，并以同周龄的WistarKyoto鼠(WKY)和未经治疗的SHR作对照。结果 单用及合用时都能使左心室指数、心肌细胞凋亡指数减少，bcl-2蛋白表达增加，Fas蛋白表达减少。但两药合用组更为明显。结论 依那普利、络沙坦合用较单用能更有效地调节抗凋亡基因与促进凋亡基因表达失衡，减少心肌细胞凋亡，阻止心脏重构的发展。

Study of a Combination Therapy with Enalapril and Losartan in Modification of Myocyte Apoptosis in Spontaneous Hypertensive Rats

Objective To detect the influence on left ventricular hypertrophy (LVH) and cardiac myocyte apoptosis in spontaneous hypertension rats (SHR) that received either enalapril and losartan alone or combination of two chemicals,and to analyze the differences between single and combined therapy.Methods Forty male SHRs of 18 weeks old were randomly assigned to 4 groups.One group was blank control; the other 3 groups were received enalapril,losartan alone and combination of enalapril and losartan.The fifth group of 8 Wiatar Kyoto rats aged 18 weeks was set up as normal control.After 16 weeks,cardiac index,left ventricular index,left ventricle wall thickness and diameter of myocardial cell were recorded.TUNEL method was applied to detect cells of apoptosis and calculate apoptosis index (AI).S-P staining was used to detect expression of bcl-2 and Fas.Results Each of three regimens has effect in reversing left ventricular hypertrophy,and the combined therapy seemed to be superior to either of two drugs alone.The superiority of combined therapy can also be seen in reducing cardiac apoptosis and an over-expression of Fas and enhancing expression of bcl-2 protein.Conclusions The combined therapy of enalapril and losartan is more effective in reversing left ventricular hypertrophy and modulating apoptosis-related gene expression than either of the drugs alone.