钙调神经磷酸酶信号通路参与充血性心力衰竭患者心肌重塑的机制

Mechanism of Calcineurin Pathway Involved in Myocaridal Remodeling in Patients With Congestive Heart Failure

目的:探讨钙调神经磷酸酶(CaN)信号通路参与充血性心力衰竭患者心肌重塑的机制。方法:选择慢性风湿性二尖瓣病变接受二尖瓣置换术的充血性心力衰竭患者39例,分为心功能Ⅱ级组12例,心功能Ⅲ级组15例,心功能Ⅳ级组12例;正常对照组38例(其中8例来自意外伤亡的器官捐献者,30例为健康体检者)。苏木素-依红染色检查心肌组织病理变化,免疫沉淀法测心肌组织CaN、活化T细胞核因子(NFAL)、锌指转录因子(GATA4)磷酸化及蛋白表达以及α-骨骼肌蛋白(α-skeletal-actin)表达,RT-PCR检测肌球蛋白重链信使核糖核酸(β-MHC mRNA)表达。结果:充血性心力衰竭患者心肌呈典型的重塑心肌的病理改变。充血性心力衰竭患者心肌组织CaN磷酸化、GATA4磷酸化、α-skeletal-actin蛋白表达及β-MHC tuRNA表达明显高于正常对照组,随心功能恶化,其表达逐渐增加(P <0．05或0．01);NFAT3磷酸化随心功能恶化而减弱(P<0．05或0．01)。结论:CaN信号通路在充血性心力衰竭患者心肌重塑机制中可能起着重要的作用。

Objective：To investigate the involvement of calcineruin （CaN） signal pathway in myocardial remodeling mechanism in patients with congestive heart failure（CHF）. Methods： Thirty-nine CHF patients with different NYHA classes were randomly selected and 38 healthy controls were randomly enrolled in this study. Myocardial pathological changes were determined by HE staining. Protein expression and phosphorylation CaN, nuclear factor of activated T cells （ NFAT3 ） , zinc finger transcription factor （ GATA4 ） in myocardial tissues,and protein expression of α-skeletal-actin were detected with immunoprecipitation assay. The mRNA expression of β-myosin heavy chain （β-MHC） was measured by RT-PCR. Results：Pathological changes of myocardial tissues in CHF patients with valvular heart disease showed typical myocardial remodeling. Hypertrophy was dominant at early stage of congestive heart failure. At end stage the characteristics included disordered alignament of the myocytes, the discontinuity and dissolving of cardiomyofibrills, destroyed subcellular organs,and the hyperplasia of interstitial tissue. Compared to NYHA functional class Ⅰ group, phosphorylation of CaN and GATA4, protein expression of α- skeletal-actin,and β-MHC mRNA expression in myocardial tissues were much higher in CHF group, and their expressions were positively correlated with the serverity of CHF（P 〈0. 05 or 0. 01 ）. Phosphorylation of NFAT3 were negatively correlated with severity of CHF（P 〉0, 05 or 0. 01 ）. Conclusion ： CaN signal pathway may play important roles in the myocardial remodeling in patients with congestive heart failure.