PTEN在心力衰竭心肌MAPK/PKC信号通路的作用

目的 观察充血性心力衰竭病人心肌重构病理过程中肿瘤抑制因子PTEN（phosphatase and tensin homolog tumor suppressor,PTEN）及丝裂原活化蛋白激酶（mitogen-activated protein kinase,MAPK）与蛋白激酶C（protein kinase C,PKC）的作用.方法 通过手术取材,选择因瓣膜性心脏病接受二尖瓣置换术的心力衰竭病人39例,正常对照38例（其中8例来自意外伤亡的器官捐献者）.竞争蛋白结合法检测心肌组织PKC及MAPK活性,免疫沉淀法检测PTEN蛋白表达.结果 心力衰竭病人心肌组织呈典型的重构心肌的病理改变.心肌组织PTEN表达蛋白光吸收（absorbance,A）与β肌动蛋白光吸收比值（PTEN/β-actin）随心功能恶化而降低,各心力衰竭组与正常组相比,差异有统计学意义（P＜0.01）;相反,心力衰竭病人心肌组织PKC和MAPK活性明显高于对照组（P＜0.01）,并随心功能恶化其表达逐渐增加,各心力衰竭组与正常组比较,差异有统计学意义（P＜0.01）.结论 PTEN及MAPK与PKC信号通路共同参与调节CHF病人心肌重构的病理过程,PTEN在心肌重构病理过程中起负性调节作用.

Impact of PTEN on mitogen activated protein kinase and protein kinase C in myocardium of patients with congestive heart failure

Objectives To investigate the roles of phosphatase and tensin homolog tumor suppressor(PTEN),mitogen-activated protein kinase(MAPK)and protein kinase C(PKC) signal transduction pathways in myocardium remodeling in patients with congestive heart failure. Methods Thirty-nine patients with congestive heart failure(CHF)at different levels according to NYHA cardiac function classification were randomly selected and 38 healthy persons were included as controls. Pathologic and morphologic studies on 8 control subjects were observed by optical microscope. Immunoprecitipation was used to assay the protein expression and phosphorylation of PTEN. Activity of PKC and MAPK were determined using competive protein binding method. Results Pathologic changes of myocardial tissues in CHF with valvular heart disease showed typical myocardial remodeling. PTEN protein expressions in CHF groups were higer than those of control group and negatively correlated to the levels of CHF(P<0.01);On the contrary, activities of MAPK and PKC in CHF groups were higher than those of control group and positively correlated to the levels of CHF(P<0.01). Conclusions Both PTEN and MAPK/PKC signal pathways involve in the pathogenesis of myocardial remodeling in CHD patients with valvular heart disease, which play an important role in the pathogenesis of myocardial hypertrophy. PTEN may be play a negative regulation role in the process of myocardial remodeling.