三类降压药物对高血压大鼠心肌细胞凋亡及左室重构的对比研究

目的 :评价氯沙坦、福辛普利、氨氯地平对自发性高血压大鼠 (SHR)心肌细胞凋亡及左室重构的效应。方法 :将 40只 16周龄SHR随机分为氯沙坦治疗组 (SHR -L)、福辛普利治疗组 (SHR -F)、氨氯地平治疗组 (SHR -A)及空白对照组 (SHR -C)。采用末端脱氧核糖核苷酸转移酶介导dUTP缺口末端标记、放免及病理检查方法对SHR治疗 8周、16周心肌细胞凋亡指数 (APOI)、血浆和组织血管紧张素II(PAngII,MAngII)及左室重构指标检测。结果 :①各治疗组治疗 8周、16周收缩压均明显下降 ,组间差异无显著性 ;各治疗组左室重量 (LVW)、左室重量指数 (LVMI)均有显著性改善 ,SHR -F组治疗 16周较其他两组LVMI显著减低。②仅SHR -F组治疗 8周APOI显著性下降 ,治疗 16周各治疗组APOI均有显著下降 ,尤以SHR -F组下降明显。③SHR -L组治疗 8周及 16周PAngII,MAngII显著增加。SHR -F组治疗 8周MAngII显著下降 ,治疗 16周SHR -F ,SHR -A两组MAngII均明显下降 ,且前组较后组下降显著 ,但对PAngII无明显影响。结论 :3药物均能有效逆转心脏肥厚及抗心肌细胞凋亡 ,其中以福辛普利显著。上述作用可能是拮抗心肌组织肾素 -血管紧张素 -醛固酮系统的效应。

Contrast of losartan,fosinopril and amlodipine on cardiomyocyte apoptosis and left ventricular remolding in hypertensive rats

Objective To investigate effects of losartan, fosinopril and amlodipine on cardiomyocyte apoptosis, cardiac remolding in the spontaneously hypertensive rats (SHR). Methods SHRs were treated with lorsartan (SHR-L), fosinopril (SHR-F ), amlodipine (SHR-A),and untreated (SHR-C) respectively for 8 and 16 weeks. Cardiomyocyte apoptotic index (APOI),left ventricular mass,left ventricular mass index(LVM,LVMI),and plasma and myocardium angiotensin II(PAng II,MAng II) concentrations were examined. Results ① The systolic blood pressure was decreased similarly in all treatment groups in 8 and 16 weeks. LVMIs were reduced significantly in all treatment groups. LVMI was significantly lower in SHR-F group than that in other two treatment groups in 16 weeks.② APOIs were decreased significantly in SHR-F group in 8 weeks and in all treatment groups,especially in SHR-F group in 16 weeks.③ Compared with SHR-C group in both periods, PAng II and MAng II were significantly increased in SHR-L group,but MAng II concentration was only decreased significantly in SHR-F group in 8 weeks,and in SHR-F and SHR-A groups in 16 weeks. Conclusion Losartan,amlodipine,and especially fosinopril can inhibit cardiomyocyte apoptosis, prevent myocardial fibrosis,and reverse heart hypertrophy. Inhibition of myocardium rennin-angiotension-aldsteron system may be the mechanism of the three drugs’ cardioprotective effects.