核因子-κB对急性缺血-再灌流心肌细胞凋亡及左室局部功能的影响

Effects of nuclear factor-κB on cell apoptosis and left ventricular segmental function in acute myocardial ischemia-reperfusion

目的探讨核因子-κB(nuclear factor-κB,NF-κB)对急性缺血-再灌流心肌细胞凋亡及左室局部功能的影响。方法24只健康杂种犬随机分为对照组(C组)、缺血-再灌流组(IR组)和缺血-再灌流加特异性NF-κB抑制剂二硫代氨基甲酸吡咯烷组(PDTC组)。IR组于第一对角支以下1 cm处套扎左冠状动脉前降支30 min,恢复血流再灌流120 min,PDTC组在心肌缺血前应用PDTC (100 mg/kg),C组游离左冠状动脉前降支不结扎。超声心动图中的应变率法测量左室局部收缩功能,Simpson’s双平面法测左室射血分数(EF),应用脱氧核甘酸末端转移酶介导的缺口末端标记法(TUNEL)测心肌细胞凋亡指数,免疫组化法及蛋白印迹(western-blot)检测心肌组织中NF-κB的表达。结果IR组NF-κB在缺血心肌组织中表达增高,显著高于C组(P<0.05),而PDTC组NF-κB表达明显减弱,显著低于IR组(P<0.05);PDTC组心肌细胞凋亡数较IR组明显减少(P<0.05);IR组左室前壁缺血节段收缩期峰值应变率(SRpeak)明显减低(P<0.01),PDTC组的应变率与IR组比较明显增高(P<0.05)。射血分数在三组间差异无统计学意义。结论NF-κB在心肌缺血-再灌流中起重要作用,PDTC通过抑制NF-κB的表达从而减轻心肌缺血-再灌流损伤,改善心功能。

Objective To probe the effects of nuclear factor kappa B （NF-κB） on cell apoptosis and left ventricular segmental function in acute ischemia reperfusion in dogs. Method Twenty-four dogs were randomly divided into three groups： without left anterior artery （LAD） ligation group （C group）, LAD was occluded 30 min following reperfusion 120 minutes in ischemical reperfusion group （IR group）, and dogs were administered with PDTC before LAD ligation in ischemical reperfusion plus pyorrole dithitocarbamate group （PDTC group）. The left ventricular segmental function was detected by echo cardiography using strain rate anlysis software. EF measured by Simpson＇s method. Cardiac myocyte apoptosis numbers were determined by terminal deoxynudeotidy transferease-mediated biotinylated deoxyuridine triphosphate nick end labehng （TUNEL）. lmmunohistochemistry and western-blot anylysis of NF-κB protein expression. Results NF-κB was obviously expression on injury myocardiumof IR group, and increased significantly in contrast to control group （P 〈 0.05）. However, the expression of NF-κB was reduced in PDTC group and had significant difference than that of IR group （ P 〈 0.05）. While apoptosis index of the ischemical myocardium of PDTC groups significantly decreased than that of IR group （ P 〈 0.05）. The peak strain rate （SRpeak） in IR group decreased obviously in contrast to C group （ P 〈 0.01）, SRpeak increased in PDTC group comparing with IR group （ P 〈 0.05）. But there was no significant difference in LVEF between three groups （ P 〉 0.05） Conclusions NF-κB might play an important role in acute myocardial ischemia repeffusion. PDTC reduces myocardial ischemia/repeffusion injury by preventing expression of factor NF-κB.