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目的研究胰岛素信号和PHLPP-1的相互抑制作用在心衰大鼠中对Akt通路的影响。方法成年雄性SD大鼠30只,随机分为3组:正常对照组、心衰模型组、胰岛素组。心衰模型组和胰岛素组采用腹腔注射阿霉素法建造大鼠心衰模型,胰岛素组给予诺和灵R腹腔注射。6周后行心脏彩超检测大鼠心功能;ELISA法检测大鼠血清尿钠肽(BNP)含量;HE染色检测大鼠心肌组织病理学改变;免疫蛋白印迹法(Western blot)检测p-Akt Ser473和PHLPP-1蛋白的表达。结果与正常对照组比较,心衰模型组心功能明显衰竭,心腔扩大,LVEF值降低(P<0.05),血清BNP含量显著增加,心肌细胞坏死、肌纤维排列紊乱、炎细胞浸润,心肌p-Akt Ser473含量降低,PHLPP-1含量增加(P<0.05);与心衰模型组比较,胰岛素组左室扩张、心功能降低明显改善,血清BNP含量降低,心肌细胞形态、纤维排列、炎症细胞浸润有所改善,p-Akt Ser473含量增加,PHLPP-1含量降低(P<0.05)。结论胰岛素信号可通过抑制PHLPP-1阻止Akt去磷酸化,从而减少心肌细胞凋亡,延缓心衰进展。
Objective To study the effect of mutual inhibition of insulin signaling and PHLPP-1 on Akt pathway in heart failure rats. Methods Thirty adult male Sprague-Dawley rats were randomly divided into three groups: normal control group, heart failure model group and insulin group. Heart failure model group and insulin group using intraperitoneal injection of doxorubicin method to establish rat heart failure model, insulin group given Novolin R intraperitoneal injection. The heart function of rats was detected by echocardiography 6 weeks later. The content of serum natriuretic peptide (BNP) was detected by ELISA. The pathological changes of myocardium were detected by HE staining. The expressions of p-Akt Ser473 and PHLPP -1 protein expression. Results Compared with the normal control group, heart failure, heart failure, heart chamber enlargement, LVEF decreased (P <0.05), serum BNP content increased significantly, myocardial necrosis, disordered muscle fibers, inflammatory cell infiltration, myocardial p- Akt Ser473 content and PHLPP-1 content increased (P <0.05). Compared with the model group, the left ventricular dilatation and cardiac function decreased significantly in the insulin group, the serum BNP level decreased, the morphology of the myocardial cells, the arrangement of the fibers, the inflammatory cell infiltration As a result, the content of p-Akt Ser473 increased and the content of PHLPP-1 decreased (P <0.05). Conclusion Insulin signaling can inhibit the dephosphorylation of Akt by inhibiting PHLPP-1, thereby reducing cardiomyocyte apoptosis and slowing the progression of heart failure.