PTEN/磷脂酰肌醇3激酶通路在心力衰竭患者心肌重构中的信号传导作用

PTEN/PI3K pathways are involved in the signal transduction of myocardial remodeling in patients with congestive heart failure

目的观察不同程度充血性心力衰竭(CHF)患者心肌组织PTEN/磷脂酰肌醇3激酶(PI3K)信号通路的表达,探讨心肌重构的信号转导机制。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CHF患者39例作为心衰(CHF)组,正常对照组38例(其中8例来自意外死亡的器官捐献者)。免疫沉淀法检测心肌组织PTEN、PI3K、蛋白激酶B(Akt)蛋白表达及其磷酸化,以及α骨骼肌蛋白的表达。结果CHF患者心肌组织呈典型的重构心肌病理改变。心肌组织PTEN蛋白表达用光密度(A)比值(PTEN/βactin)表示,正常组3.29±0.11,心功能Ⅱ级组2.56±0.19,心功能Ⅲ级组1.52±0.35,心功能Ⅳ级组0.91±0.10,各CHF组与正常组相比差异有统计学意义(P<0.05或0.01)。PI3K磷酸化A比值(PI3K/βactin),正常组0.21±0.04、心功能Ⅱ级组0.52±0.09、心功能Ⅲ级组1.12±0.29、心功能Ⅳ级组1.62±0.54;Akt磷酸化A比值(Akt/βactin),正常组0.75±0.13,心功能Ⅱ级组1.21±0.34,心功能Ⅲ级组2.45±0.71,心功能Ⅳ级组3.55±0.80,随心功能恶化,PI3K及Akt磷酸化逐渐增强(P<0.05或0.01)。α骨骼肌蛋白表达A比值(α骨骼肌蛋白/βactin),正常组0.20±0.03,心功能Ⅱ级组0.41±0.04,心功能Ⅲ级组0.82±0.09,心功能Ⅳ级组1.56±0.11,各CHF组与正常组相比差异有统计学意义(

Objective To investigate the roles of PTEN (phosphatase and tensin homologue deleted on chromosome ten)/PI3K (phosphatidylinositol 3 kinase) signal transduction pathways in myocardium remodeling in patients with congestive heart failure (CHF). Methods A small amount of papillary muscle tissue was collected during mitral valve displacement from 39 patients of mitral valve disease with CHF, 12 cases with grade Ⅱ, 15 cases with grade Ⅲ, and 12 cases with grade Ⅳ cardiac function. 30 cases of healthy persons and 8 cases of heart donors who died of accident were included as controls. Pathological examination was conducted. Immunoprecitipation was used to assay the protein expression and phosphorylation of PTEN, PI3K and Akt (protein kinase B), and protein expression of α-skeletal-actin in myocardial tissues. Results Typical myocardial remodeling was shown in the myocardial tissues from the valvular heart disease patients with CHF. Hypertrophy was dominant in the myocardial tissues at early stagy of CHF, the myocardial tissues in the end stage of CHF was characterized by disordered alignment of myocytes, discontinuity and dissolving of cardiac fiber, destroyed subcellular organs, and hyperplasia of interstitial tissue. The protein expression of PTEN [absorbance value (A) ratio of PTEN and β-actin] in control group was 3.29±0.11, grade Ⅱcardiac function was 2.56±0.19, grade Ⅲ was 1.52±0.35, grade Ⅳ was 0.91±0.10, PTEN protein expressions in CHF groups were lower than that of control group and negatively correlated to the levels of cardiac function(P<0.05 or 0.01). On the contrary, The phosphorylation of PI3K (PI3K/β-actin) in control group was 0.21±0.04, grade Ⅱcardiac function was 0.52±0.09,grade Ⅲ was 1.12±0.29,grade Ⅳ was 1.62±0.54; The phosphorylation of Akt (Akt/β-actin)in control group was 0.75±0.13,grade Ⅱcardiac function was 1.21±0.34,grade Ⅲ was 2.45±0.71,grade Ⅳ was 3.55±0.80;The protein expression of α-skeletal-actin(α-skeletal-actin/β-actin)in control group was 0.20±0.03 , grade Ⅱcardiac function was 0.41±0.04,grade Ⅲ was 0.82±0.09,grade Ⅳ was 1.56±0.11, their expressions in CHF groups were higher than that of control group and positively correlated to the levels of cardiac function (P<0.05 or 0.01). Conclusion Both the PTEN and PI3K signal pathways are involved in the pathogenesis of myocardial remodeling in CHF patients with valvular heart disease, which play an important role in the pathogenesis of myocardial hypertrophy. PTEN may play a negative regulation role in the process of myocardial remodeling.