异丙酚对大鼠离体心脏缺血再灌注时NF-κB及iNOS的影响

目的 探讨异丙酚对大鼠离体心脏缺血再灌注时核因子κB(NF-κB)及诱导型一氧化氮合酶(iNOS)的影响.方法 成年SD大鼠24只,体重200～300 g,雌雄不拘,随机分为3组(n=8):对照组(C组)、缺血再灌注组(I/R组)和异丙酚组(P组).建立Langendorff离体心脏灌注模型,K-H液平衡20 min后开始实验.C组灌注K-H液110 min;I/R组灌注K-H液20 min后,全心停灌30 min,再灌注60 min;P组用含50 μmol/L异丙酚的K-H液灌注20 min,全心停灌30 min,再用含50 μmol/L异丙酚的K-H液灌注60 min.于平衡末、再灌注10 min和60 min时测定冠状动脉流出液心肌肌钙蛋白(cTnI)浓度;于再灌注60 min时测定心肌SOD活性、MDA含量、iNOS活性及NF-κB、IκB的表达水平.结果 与C组比较,I/R组再灌注期间冠状动脉流出液cTnI浓度升高,P组再灌注期间60 min时升高(P＜0.05或0.01),I/R组心肌SOD活性降低,MDA含量增多,iNOS活性升高(P＜0.01),I/R组和P组心肌NF-κB表达升高,kB表达降低(P＜0.05或0.01).与I/R组比较,P组再灌注期间冠状动脉流出液cTnI浓度、心肌MDA含量、NF-κB表达、iNOS活性均降低,心肌SOD活性和IκB表达升高(P＜0.01).结论 异丙酚可抑制心肌NF-κB的激活,降低iNOS的活性,从而减轻大鼠离体心脏缺血再灌注损伤.

Effects of propofol on myocardial NT-κB and INOS during myocardial ischemia-reperfusion in isolated rat hearts

Objective To investigate the effects of propofol on myocardial nuclear factor kappaB(NF-κB)and inducible nitric oxide synthase (iNOS) during myocardial ischemia-reperfusion (I/R) in isolated rat hearts.Methods Twenty-four adult SD rats of both sexes weighing 200-300 g were randomly divided into 3 groups (n=8 each):group Ⅰ control (C) ; group Ⅱ I/R and group Ⅲ propofol + I/R (P).The animals were anesthetized with intrxperitoneal urethane 1.0 g/kg and their hearts were excised.The aorta was cannulated and the hearts were retrogradely pedused with oxygenated K-H solution in a Langandorff apparatus for 20 min.In group C the hearts were continuously perfused with K-H solution for 110 min.In I/R group after 20 min stabilization the hearts were made globally ischemic for 30 min followed by 60 rain reperfusion.In group P the hearts were peffused with K-H solution containing 50 μmol/L propofol for 20 min,the hearts were then made globally ischemic for 30 min followed by 60 min repedusinn with K-H solution containing 50 μmol/L propofol.Cardiac troponinI (cTnI) concentration in coronary effluent was measured at the end of 20 min stabilization before myocardial isobemia (baseline) and at 10 min(T1) and 60 min (T2) of reperfusion.Myocardial specimen was obtained frem left ventricle at 60 min of repeffusion for determination of MDA content,SOD and iNOS activity,the expression of NF-κB and IκB (by immuno-histochemistry).Results The cTnI concentration in coronary effluent was significantly higher at T1 and T2 in group I/R and at T2 in group P than in group C.The NF-κB expression was significantly higher while IκB expression was lower in I/R and P group than in group C.iNOS activity was higher in I/R group than in control group but there was no significant difference in iNOS between group P and C.Propofol administered before and after myocardial ischemia significantly attenuated I/R-induced changes listed above.Conclusion Propofol can attenuate myocardial ischemia-reperfusien injury through reducing the NF-κB activation and suppressing the iNOS activity.