舒芬太尼延迟预处理对兔心肌缺血再灌注损伤的影响

目的 探讨舒芬太尼延迟预处理对兔心肌缺血再灌注损伤的影响及其可能机制.方法 雄性新西兰白兔36只,8～18月龄,体重2.0～2.4 kg,随机分为5组,心肌缺血再灌注组(IR组,n=9):静脉注射生理盐水2 ml/kg;舒芬太尼5μg/kg延迟预处理组(S1组,n=6)和10 μg/kg延迟预处理组(S2组,n=9):分别静脉输注舒芬太尼5、10 μg/kg,速率10 ml/h:纳洛酮组(N组,n=6):静脉输注纳洛酮10 mg/kg,速率10 ml/h;纳洛酮+舒芬太尼组(NS组,n=6):先静脉输注纳洛酮10 mg/kg,再静脉输注舒芬太尼5 μg/kg,速率均为10 ml/h.于给药结束后24 h时采用阻断左冠状动脉前降支30 min,再灌注3 h的方法 制备兔心肌缺血再灌注模型.于给药前(基础状态)、缺血30 min、再灌注1、2、3 h时记录心率(HR)、平均动脉压(MAP),并计算心率血压乘积(RPP);于再灌注3 h时测定心肌缺血面积和梗死面积,同时IR组和S2组采用TUNEL法测定心肌细胞凋亡情况,计算凋亡指数,并采用免疫组织化学法测定心肌Bcl-2和Bax的表达水平.结果 与基础值比较,各组心肌缺血再灌注时MAP、RPP下降,S2组HR降低(P<0.05),组间比较异差异无统计学意义(P>0.05);与IR组比较,S1组、S2组和NS组梗死面积减小(P<0.05),N组梗死面积无统计学意义(P>0.05),S2组凋亡指数降低,心肌Bcl-2表达上调,Bax表达下调(P<0.05);与S1组比较,S2组梗死面积减小(P<0.05),N组和NS组梗死面积增大(P<0.05);与S2组比较,N组和NS组梗死面积增大(P<0.05).结论 舒芬太尼延迟预处理可减轻大鼠心肌缺血再灌注损伤,其机制可能与激活阿片受体,抑制心肌细胞凋亡有关.

Effect of delayed preconditioning with sufentanil on myocardial ischemia and reperfusion injury in rabbits

Objective To investigate whether delayed preconditioning with sufentanil can protect against myocardial ischemia and reperfusion (IR) injury and the possible mechanism. Methods Thirty-six male New Zealand white rabbits 8-18 months old weighing 2.0-2.4 kg were used in this study. The animals were anesthetized with iv etomidate 2 mg/kg, tracheostomized and mechanically ventilated (VT 10-12 ml/kg, RR 20-25 bpm, FiO2 100%). Carotid artery and jugular vein were cannulated for BP and HR monitoring and fluid administration.Myocardial ischemia was induced by 30 min of occlusion of anterior descending branch of left coronary artery followed by 3 h of reperfusion. The animals were randomly assigned to one of 5 groups based on the sufentanil and/or naloxone the animals received 24 h before myocardial ischemia: group Ⅰ received normal saline (group IR,n=9); greup Ⅱ sufentanil 5 μg/kg (group S1, n=6); group Ⅲ sufentanil 10 μg/kg (group S2, n=9); group Ⅳ naloxone 10 mg/kg (group N, n =6) and group Ⅴ naloxone 10 mg/kg + sufentanil 5 μg/kg (group NS, n =6). Myocardial infarct size was measured using triphenyl tetrazolium (TIC) staining. Myocardial apoptosis was detected by TUNEL, and Bcl-2 and Bax protein expression was determined by immuno-histochemistry in group IR and S2. Results Sufentanil produced a dose-dependent reduction in infarct size as compared with group IR.Naloxone had no effect on infarct size but partially abolished sufentanil-induced cardio-protection. Sufentanil significantly decreased myocardial apoptosis and Bax protein expression but increased Bcl-2 protein expression as compared with group IR. Conclusion Sufentanil produces a delayed preconditioning against myocardial IR injury through activating opioid receptors and inhibiting cadiomyocyte apoptosis.