摘要
目的观察雷米普利对大鼠缺血/再灌注心肌细胞凋亡及凋亡相关基因表达的影响。方法大鼠口服雷米普利(1 mg.kg-1)或等剂量生理盐水,24 h后制备心肌缺血30m in再灌注120 m in模型,用2,3,5-三苯基氯化四氮唑(TTC)染色法测定心肌梗死范围,用脱氧核糖核苷酸末端转移酶介导的dUTP缺口末端标记法(TUNEL)和DNA琼脂糖凝胶电泳技术检测心肌细胞凋亡并用免疫组化方法测定抑凋亡基因(Bc l-2)和促凋亡基因(Bax)的表达。结果与对照组相比,雷米普利组由缺血/再灌注损伤引起的心肌梗死范围缩小,细胞凋亡指数减少且DNA琼脂糖凝胶电泳呈现减弱的DNA梯形图谱,Bc l-2表达增加以及Bc l-2/Bax比值增加。结论雷米普利通过减少/缺血再灌注心肌细胞坏死和凋亡以及上调抑凋亡基因Bc l-2的表达发挥心脏保护作用。
Aim To observe the effect of ramipril on ischemia-reperfusion induced apoptosis of cardiomyocytes and expression of apoptosis-related genes. Method Male Wistar rats were subjected to 30 min of myocardial ischemia and 120 min of reperfusion. Rats were randomized to receive vehicle or ramipril (1 mg · kg^-1) orally 24 h before surgery. Myocardial infarct size was measured using the staining agent 2,3,5-triphenyl tetrazolium chloride (TTC). Cardiomyocyte apoptosis was assessed using terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and confirmed with detection of DNA ladder formation. The expression of antiapoptotic gene (Bcl-2) and proapoptotic gene (Bax) was determined by immunohistochemistry. Results At the end of reperfusion, infarct size was reduced by ramipril. TUNEL assay and DNA-laddering study demonstrated that cardiomyocyte apoptosis was attenuated in ramipril-treated hearts, correlating with increased expression of Bcl-2 and ratio of Bcl-2/Bax. Conclusion Ramipril exerts cardioprotection by decreasing the ischemia-reperfusion induced necrosis and apoptosis of cardiomyocyte and increasing the expression of Bcl-2 and ratio of Bcl-2/Bax.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2006年第5期625-628,共4页
Chinese Pharmacological Bulletin
基金
天津市自然科学基金资助项目(No003506811)