钙调神经磷酸酶参与心衰患者心肌重构的信号转导

Calcineurin is involved in signal transduction of myocaridal remodeling in patients with congestive heart failure

目的:探讨血管紧张素Ⅱ(AngⅡ)介导的钙调神经磷酸酶(CaN)信号通路参与心力衰竭(CHF)患者心肌重塑的机制。方法:选择因瓣膜性心脏病接受二尖瓣置换术的CHF病人39例,正常对照38例(其中8例来自意外伤亡的器官捐献者)。彩色多普勒超声心动图仪检测心脏扩大和心功能参数。放免法检测血浆及心肌组织AngⅡ浓度,免疫沉淀法测心肌组织CaN、活化T细胞核因子(NFAT3)、锌指转录因子(GATA4)磷酸化及蛋白表达,RT-PCR检测肌球蛋白重链(β-MHC)mRNA表达。结果:AngⅡ分别与心脏扩大参数呈显著正相关,而与心功能参数呈显著负相关。CHF患者心肌组织CaN蛋白表达、CaN磷酸化、GATA4蛋白表达及β-MHCmRNA表达明显高于对照组,随心功能恶化其表达逐渐增加;NFAT3磷酸化随心功能恶化而减弱。结论:肾素血管紧张素系统(RAS)激活的CaN信号通路在CHF患者心肌重构机制中可能起重要作用。

AIM： To investigate the involvement of ealeineruin （CaN） signal pathway mediated by angiotension Ⅱ （Ang Ⅱ ） in the myocardial remodeling mechanism in patients with congestive heart failure （CHF）. METHODS： 39 patients of mitral valve disease with CHF were randomly selected and 30 cases of healthy persons were included as controls. Cardiac function parameters were measured by echocardiography. Concentration of Ang Ⅱ in plasma and myocardial tissues were determined by radioimmunoassay. Immunoprecitipation was used to assay the protein expression and phosphorylation CaN, nuclear factor of activated T cells （ NFAT3 ） ,zinc finger transcription factor （ GATA4 ） in myocardial tissues. The mR- NA expression of β - myosin heavy chain （ β - MHC） was measured by RT - PCR. RESULTS： The Ang Ⅱ concentrations in patients with CHF were positively correlated with the parameters of the cardiac dialtion respectively, but negatively correlated with the paremeters of cardiac function. Compared to the control group, protein of CaN and GATA4 , phosphorylation of CaN, and β - MHC mRNA expression in myocardial tissues in CHF groups were highly expressed and their expression were positively correlated to the levels of CHF, but the phosphorylation of NFAT3 was negatively correlated with the levels of CHF. CONCLUSION： CaN signal pathway may play important roles in the myocardial remodeling in CHF.