摘要
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。
Aim To invesitgate the effect of PTEN （ phosphatase and tensin homologue deleted on chromosome ten）/PI3 K （ phosphatidylinositol 3 kinase） signal transduction pathway in hypertrophied myocardium mediated by overloaded pressure in rats, and the effect of angiotension Ⅱ （ Ang Ⅱ ） receptors （ AT1, AT2 ） antagonists on it. Methods Overloaded pressure hypertrophied myocardium rat model was established by abdominal arota constriction. Thirty two male wistar rats were divided randomly into four groups, namely sham-operated group, banding group, valsartan group （banding group and valsartan administation）, and PD123319 group （banding group and PD123319 administration）. Ang Ⅱ concentration in plasma and left ventricular myocardium were measured by radioimmunoassays. Cardiac index was measured and HE staining was performed with left ventricular myocardium, immunoprecitipation was used to assay the protein expression and phosphorylation of PTEN, PI3K and Akt （Protein kinase B）, protein expression of α-skeletal-actin in myocardial tissues. Results Ang Ⅱ concentration in serum and left ventricular myocardium tissue in banding group was higher than that in sham-operated group, valsartan group andPD123319 group（P 〈 0. 01 ） ; Ang Ⅱ concentration in serum in valsartan group was higher than that in banding and PD123319 groups（P 〈0. 05）, but it was lower in left ventricular myocardium tissue （P 〈 0. 05 ）. Phosphorylation of PI3K/Akt in left ventricular myocardium fissure in banding group was higer than that in sham-operation group（P 〈 0. 01 ） , the expression of PTEN was lower than that in sham-operation group（P 〈 0. 01 ） ; Phosphorylation of PI3K/Akt in valsartan group was obviously lower than that in banding and PD123319 groups （P 〈 0. 05 ）, and PTEN protein expression in valsartan group was higher than that in banding and PD123319 groups（P 〈0. 05）, but there were no big differences between banding and PD123319 groups （ P 〉 0. 05 ）. Conclusions PTEN/ PI3Ksignal pathway is involved in myocardium hypertrophy in overloaded pressure rat model. The up-regulations of PI3K/Akt and down regulation of PTEN are mediated via AT1 and can be reduced by AT1 receptor antagonists.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2006年第7期823-827,共5页
Chinese Pharmacological Bulletin
