二氮嗪对异丙肾上腺素诱发的大鼠心肌缺血损伤的保护作用

Effects of Diazoxide on Myocardial Ischemia Injury Induced by Isoproterenol in Rats

目的 :评价线粒体三磷酸腺苷敏感性钾通道 (mitoKATP)开放剂二氮嗪 (diazoxide ,Diaz)对大鼠心肌缺血损伤的保护作用。 方法 :选用Wistar大鼠 3 6只 ,分为对照组 8只、异丙肾上腺素 (ISO)组 10只、二氮嗪 10mg/kg组 9只和二氮嗪2 0mg/kg组 9只。用ISO 5mg/kg皮下注射复制大鼠心肌缺血损伤模型 ,2 4h后采血测定血清乳酸脱氢酶 (LDH)和肌酸激酶 (CK)活性及乳酸含量 ,同时监测心电图、血压和心率的变化 ,并观察心肌组织形态学改变。 结果 :ISO引起大鼠心肌缺血损伤时 ,ISO组与对照组比较 ,血清LDH、CK活性和乳酸含量明显增加 ,有极显著性差异 (P <0 0 1) ,组织形态学也发生明显改变 ,心肌细胞损伤严重 ,有极显著性差异 (P <0 0 1)。预先口服二氮嗪 10～ 2 0mg/kg可逆转血清LDH、CK和乳酸的升高 ,有显著性差异 (P <0 0 5～ 0 0 1) ,减轻心肌细胞损伤程度。二氮嗪 10mg/kg不影响收缩压和心率。 结论

Objective:To evaluate the effects of mitochondrial adenosine trphosphate(ATP) sensitive potassium channel opener diazoxide on myocardial ischemia injury in rats Methods:A myocardial ischemia injury model on rat is established by subcutaneous injection of isoproterenol 5 mg/kg The levels of serum lactate dehydrogenase(LDH),creatine kinase (CK) and content of lactic acid were measured 24h later Electrocardiographic analysis and systolic blood pressure as well as histological examinations were performed Results:Compared with the controls,the levels of serum LDH,CK and lactic acid were significantly increased (p<0 01) Morphologically,severe myocardial injury was found Oral administration of diazoxide at a concentration of 10 20*! mg/kg reversed increased serum LDH,CK,lactic acid (p<0 05 0 01) and reduced the severity of myocardial injury Diazoxide 10*! mg/kg had no effect on systolic blood pressure and heart rate Conclusion:These results suggest that diazoxide has a cardioprotective effect on isoproterneol induced myocardial injury in rats