PTEN/磷脂酰肌醇3激酶通路参与高压力负荷心肌肥厚的机制

目的探讨压力负荷下心肌组织PTEN(phosphataseand tensin homologue deleted on chromosom e ten)/磷脂酰肌醇3激酶(PI3K)信号通路的变化,及血管紧张素受体(angio-tensinⅡreceptors)AT1及AT2拮抗剂对它的影响,探讨心肌肥厚的信号转导机制。方法腹主动脉缩窄法建立大鼠高压力负荷心肌肥厚模型,实验动物分为手术组(n=8);缬沙坦(valsartan)组(n=8):手术组+valsartan(1 mg.kg-1.d-1);PD123319组(n=8):手术组+PD123319(30 mg.kg-1.d-1);假手术组(n=8)。放免法检测心肌及血浆AngⅡ浓度,测定心指数并对心肌组织作HE染色,免疫沉淀法检测心肌组织PTEN、PI3K、蛋白激酶B(Akt)蛋白表达及磷酸化,α-骨骼肌蛋白(-αskeletal actin)蛋白表达。结果大鼠术后14 d,valsartan组血浆AngⅡ浓度高于假手术组及PD123319组(P<0.05),valsartan组心肌AngⅡ浓度则低于假手术对照组及PD123319组(P<0.05)。手术组PI3K/Akt磷酸化高于假手术组(P<0.01),手术组PTEN蛋白表达低于假手术组(P<0.01);valsartan组PI3K/Akt磷酸化低于手术组及PD123319组(P<0.05),valsartan组PTEN高于手术组及PD123319组(P<0.05),PI3K/Akt磷酸化及PTEN蛋白表达量手术组与PD123319组间差异无显著性(P>0.05)。结论高压力负荷下,PTEN蛋白表达降低,心肌组织PI3K/Akt磷酸化增强,参与心肌重构的病理过程,且主要通过AT1起作用。

PTEN/PI3K signal pathway involved in myocardial hypertrophy mediated overloaded pressure in rats

Aim To invesitgate the effect of PTEN(phosphatase and tensin homologue deleted on chromo-some ten) /PI3K(phosphatidylinositol 3 kinase) signaltransduction pathway in hypertrophied myocardium me-diated by overloaded pressure in rats,and the effect ofangiotensionⅡ(AngⅡ) receptors(AT1,AT2) antag-onists on it.Methods Overloaded pressure hypertro-phied myocardiumratmodel was established by abdom-inal arota constriction.Thirty two male wistar rats weredivided randomly into four groups,namely sham-opera-ted group,banding group,valsartan group(bandinggroup and valsartan administation),and PD123319group(banding group and PD123319 administration).AngⅡconcentration in plasma and left ventricular myo-cardium were measured by radioimmunoassays.Cardiacindex was measured and HE staining was performedwith left ventricular myocardium,immunoprecitipationwas used to assay the protein expression and phospho-rylation of PTEN、PI3K and Akt(Protein kinase B),protein expression ofα-skeletal-actin in myocardial tis-sues.Results AngⅡ concentration in serum and leftventricular myocardium tissue in banding group washigher than that in sham-operated group,valsartangroup andPD123319 group(P<0.01);AngⅡ con-centration in serum in valsartan group was higher thanthat in banding and PD123319 groups(P<0.05),butit was lower in left ventricular myocardium tissue(P<0.05).Phosphorylation of PI3K/Akt in left ventricularmyocardium tissure in banding group was higer thanthat in sham-operation group(P<0.01),the expres-sion of PTEN was lower than that in sham-operationgroup(P<0.01);Phosphorylation of PI3K/Akt invalsartan group was obviously lower than that in ban-ding and PD123319 groups(P<0.05),and PTENprotein expression in valsartan group was higher thanthat in banding and PD123319 groups(P<0.05),butthere were no big differences between banding andPD123319 groups(P>0.05).Conclusions PTEN/PI3Ksignal pathway is involved in myocardium hyper-trophy in overloaded pressure rat model.The up-regu-lations of PI3K/Akt and down regulation of PTEN aremediated via AT1 and can be reduced by AT1 receptorantagonists.