磷酯酶A2抑制剂DTNB对大鼠心肌 缺血再灌注心律失常的影响

目的:研究非钙依赖性的磷脂酶A₂ (PLA₂)和ATP敏感性钾通道(K_ATP)在大鼠心肌缺血再灌注(I/R)心律失常中的作用。方法:结扎大鼠左冠状动脉前降支造成缺血10 min,然后放开再灌注10 min。在心肌缺血前5 min分别给予PLA₂抑制剂5,5'-dithio-bis(2-nitrobenzoic acid)(DTNB)(16 mg/kg),K_ATP开放剂pinacidil(0.2 mg/kg),K_ATP阻断剂glibenclamide(0.3 mg/kg)。结果:与对照组相比,DTNB可降低心律失常评分、磷酸肌酸激酶(CPK)和乳酸脱氢酶 (LDH)值(P＜0.05);而glibenclamide对I/R心律失常无影响,但升高CPK,LDH值(P＜0.05);与glibenclamide组比,在glibenclamide阻断K_ATP后,DTNB可引起致死性心律失常,并可升高LDH值(P＜0.05);pinacidil可完全抑制I/R引起的室颤和室速。结论:PLA₂抑制剂DTNB可减轻I/R损伤,表明PLA₂在I/R心律失常中起着重要作用,同时也表明激活的K_ATP具有抗I/R心律失常的作用。但DTNB对抗I/R心律失常的作用与K_ATP的关系仍有待进一步研究。

The effect of phospholipase A2 inhibitor DTNB on the rat ischemia reperfusion arrhythmia

AIM: To determine the effects of phospholipase A₂ (PLA₂) and K_ATP on rat ischemia/reperfusion(I/R)-induced arrhythmia. METHODS: Myocardial ischemia and reperfusion were produced by occlusion and reirregation of the left anterior descending artery(LAD). An inhibitor of PLA₂, 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) (16 mg /kg), a K_ATP opener pinacidil (0.2 mg/kg), a K_ATP blocker glibenclamide (0.3 mg/kg) was used 5 min prior to 10 min regional ischemia and 10 min reperfusion. RESULTS: DTNB (16 mg/kg) reduced the scores of arrhythmia, creatine kinase (CPK) and lactate dehydrogenase(LDH) (P＜0.05). Glibenclamide had no effect on I/R arrhythmia, but increased CPK and LDH (P＜0.05). After K_ATP was blocked by glibenclamide, DTNB led to lethal ventricular fibrillation and increase LDH, higher than without DTNB (P＜0.05). Pinacidil depleted ventricular fibrillation and ventricular tachycardia. CONCLUSIONS: PLA₂ inhibitor DTNB enhances membrane stability both in structure and function, so that reduces myocardial damage caused by I/R, and suggests that PLA₂ plays an important role on myocardial I/R arrhythmia, and also implies that activated K₊ATP prevents rats from I/R arrhythmia under condition of our experiments, but the relationship between DTNB protective effect and K_ATP activity remains indefinite.