钙蛋白酶参与心力衰竭患者心肌重构的信号传导

Calpain involved in signal transduction of myocardial remodeling in patients with congestive heart failure

目的 探讨钙敏感的信号物质钙蛋白酶 (calpain)对心力衰竭 (心衰 )患者心肌重构信号传导的调控。方法 选择因二尖瓣狭窄伴关闭不全心脏病接受二尖瓣置换术的心衰患者 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检测心功能参数,放免法检测心衰患者血浆及心肌组织血管紧张素Ⅱ含量,免疫印迹法检测心肌组织calpain、钙调神经磷酸酶(CaN)的抑制蛋白(cain/cabin1), cain/cabin1降解产物 (cain/cabin1Δ)蛋白表达、CaN磷酸化。结果 心衰患者血浆及心肌组织血管紧张素Ⅱ浓度、心肌组织u calpain、m calpain、cain/cabin1降解产物cain/cabin1Δ蛋白表达及CaN磷酸化明显高于对照组,且随心功能恶化逐渐增加, cain/cabin1蛋白表达随心功能恶化逐渐降低。结论 心衰患者通过calpain降解cain/cabin1进而激活CaN信号通路,提示其在肾素 血管紧张素系统等介导的心肌重构中起一定作用。

Objective To investigate the regulation of calcium sensitive signal substance calpain in signal transduction of myocardial remodeling in patients with congestive heart failure Methods All 39 congestive heart failure (CHF) patients with rehumatic mitral valve stenosis disease were selected and 38 cases of healthy persons were included as controls Cardiac function parameters were measured by echocardiography The concentration of angiotensionⅡ (AngⅡ) in plasma and myocardial tissues was determined by radio immunoassay(RIA) Western blot was used to assay the protein expression of calpain, cain/cabin 1, cain/cabin 1Δ, and calcineurin (CaN) phosphorylation Results The AngⅡ concentrations in the plasma and myocardial tissues in patients with CHF were higher than those in the control group Meanwhile the AngⅡ concentrations positively correlated to the parameters of the cardiac dilation respectively but negatively correlated to the parameters of cardiac function Pathological changes of myocardial tissues in CHF with valvular heart disease showed typical myocardial remodeling The hypertrophy was dominant at early stagy of CHF, while at the end stage the characteristics include disordered alignament of the myocytes, the discontinity and dissolving of cardiomyofibrills, destroyed subcellular organs, and the hyperplasia of interstitial tissue Compared to the control group, u calpain, m calpain, and cain/cabin 1Δ protein expression, CaN phosphorylation in myocardial tissues in CHF groups were highly expressed and their expressions were positively correlated to the severity of CHF The expression of cain/cabin1 deceased and its expression was negatively correlated to the severity of CHF Conclusion The degragation of cain/cabin 1 by calpain may play an important role by causing the activation of CaN signal pathway in myocardial remodeling mediated by renin angiotension system in CHF