干预DAG-PKC信号转导通路对糖尿病大鼠心肌细胞JNK1和IRS1基因表达的影响

Intervention of DAG-PKC pathway affects JNK1 and IRS1 expression in diabetic rat myocardium

目的干预二酰甘油-蛋白激酶C(DAG-PKC)信号转导通路后观察JNK1、IRS1等在糖尿病大鼠心肌中的表达情况。方法采用HE染色,masson染色、电镜观察大鼠心肌的病理变化,应用免疫组化、Real-Time PCR检测PKCβ2、JNK1及IRS1在大鼠心肌的表达情况。结果糖尿病模型组PKCβ2、JNK1、p-JNK、IRS1表达明显高于对照组,干预DAG-PKC信号转导通路后明显下调其表达水平。结论 DAG-PKC通路可能是通过G蛋白受体和胰岛素受体途径的共同信号点JNK1影响下游的信号传导而导致糖尿病心肌病的发生发展,DAG-PKC-JNK1-IRS1-Akt/PKB-mTOR-p70S6K1等一系列信号位点可能是DAG-PKC信号转导通路引起糖尿病心肌病可能的潜在途径。

Objective To observe the expression of JNK1 and IRS1 in the myocardium of diabetic rats after the intervention of the DAG PKC signal transduction pathway. Methods We observed the pathological changes of the rat myocardium with HE staining, Masson staining, and electron microscopy. We detected the JNK1 and IRS1 expression in rat cardiomyocytes using immunohistochemistory and Real Time PCR. Results The expression of PKCI32, JNKI,p-JNK and IRS1 was significantly higher in the DM group , but significantly lowered its expression levels after the intervention of the DAG PKC signal transduction path-way. Conclusion DAG-PKC signaling pathway may influence the downstream signaling through junl a com-mon signal of the G-protein receptor and the insulin receptor pathway, thus leading to the development of diabetic cardiomyopathy. DAG-PKC-JNK1-IRS1-Akt / PKB-mTOR-pTOS6K1 may be critical siteson the DAG PKC signal transduction pathway to induce diabetic cardiomyopathy.