充血性心力衰竭病人心肌细胞凋亡及Fas／FasL系统的调节作用

目的 观察充血性心力衰竭（CHD）病人心肌细胞是否存在细胞凋亡以及Fas/FasL蛋白、caspase-3和心肌氧化性应激的调节作用。方法 实验以进行常规CPB的无肺动脉高压的ASD病人为对照组（n＝5），以合并CHD的RHD病人为观察组（n＝5）。体外循环术前留取右心室标本。用原位TUNEL技术检测凋亡心肌细胞。用流式细胞仪技术测定右心室Fas和FasL蛋白表达。用Z－DEVD－AMC底物降解法和TBARS方法分别测定右心室心肌caspase-3酶活性和脂质过氧化物含量（MDA）。结果 RHD病人右心室心肌细胞凋亡数、caspase-3活性、MDA以及Fas、FasL蛋白表达均明显高于ASD病人（P分别咪0．026、0．013，0．002，0．004和0．033）。结论 心肌细胞凋亡参与CHD的病理生理过程。CHD病人的心肌细胞凋亡与心肌细胞Fas、FasL蛋白表达上调、caspase-3激活以及心肌氧化性应激增高有关。

Myocardiocyte apoptosis in patients with CHD and modulation of Fas/FasL and caspase-3 pathway

Objective To investigate if there exists myocyte apoptosis in human failing heart and the modulation of Fas, FasL proteins,caspase 3 pathways and the role of myocardial oxidative stress in this setting. Methods Right ventricular samples from patients with ASD without pulmonary artery hypertension undergoing conventional CPB were used as control group( n =5);samples from patients with CHD undergoing mitral valve replacement were used as observation group( n =5). In situ TUNEL technique was used for detecting apoptotic myocytes.Flow cytometry were employed for detection of expression of Fas and FasL proteins in right ventricle.ZDEVD AMC substrate cleavage and TBARS methods were used to examine the activity of caspase 3 and the content of lipid peroxide in right ventricular myocardium,respectively. Results The number of TUNEL positive myocyte nuclei,expression of Fas and FasL,caspase 3 activity and the lipid peroxidation in right ventricular myocardium in CHD patients were all significantly greater than those in ASD patients( P <0 026,0 013,0 002,0 004 and 0 033,respectively). Conclusion It shows that there exists myocardiocyte apoptosis in human failing heart.In addition,myocardiocyte apoptosis in CHD patients is associated with upregulation of expression of Fas and FasL proteins,activation of caspase 3 and enhancement of oxidative stress in the myocardium.