糖尿病大鼠额叶脑神经细胞中ERK1/2及其下游底物Elk-1磷酸化表达状态的研究

摘要

Objective To explore the pathogenesis of diabetic encephalopathy,phosphorylation of the extracellular signal regulated kinase 1/2(ERK1/2)and Elk-1 in frontal cortex neurons from rats with diabetes. Methods Type I diabetic rats was induced by STZ injection. HE staining was applied in this study to observe the pathological changes of the frontal lobe of diabetic rats and immunohistochemistry was used to detect the expression of phosphorylated ERK1/2 and the expression of its down-stream substrate Phospho-Elk-1 in neurons. Results At the 4th week and the 8th week after STZ injection,the positive rates of phosphorylated-ERK1/2 expression in the neurons of frontal cortex and the rates of phospho-Elk-1MAPK in the frontal cortex and gray matter nucleus neurons from diabetic rats were signficantly higher in the diabetic group than those in the control group,respectively (P<0.05). And the positive rates of both of phosphorylated-ERK1/2 and phospho-Elk-1 MAPK in the neurons from 4th week or the 8th week diabetic groups were higher than those from the 3rd day and from the 2th week of diabetic rats,respectively. The positive rate of phosphorylated ERK1 /2 and phosphorylated Elk-1MAPK in the frontal cortex nucleus from the 8th week diabetic group was signficantly higher than that from the 4th week(P<0.05). The positive rates of phosphorylated ERK1/2 in frontal cortex neurons from diabetic rats in the 2nd,4th,8th week after model establishment were signficantly higher than those in the control group and the third day after model establishment(P<0.05). With the extension of the diabetic states,the positive rate of phosphorylated ERK1/2 increased gradually(P<0.05). Conclusion The abnormal activation of ERK1/2 signal transduction pathway existed in the frontal lobe nerve cells from 4th and 8th weeks of diabetic rats.%目的 研究糖尿病大鼠额叶神经细胞中细胞外信号调节蛋白激酶(extracellular regulated protein kinases, ERK1/2)、底物磷酸化ets样基因1(Elk-1)的磷酸化表达状态,以探讨糖尿病脑病的发病机制.方法 应用链脲佐菌素(streptozotocin,STZ)诱导制备糖尿病大鼠模型,通过组织学、免疫组化染色,对比观察糖尿病大鼠额叶脑组织的病理改变及神经细胞中磷酸化ERK1/2及下游作用底物Phospho-Elk-1的表达情况.结果 制模后第4周和第8周,糖尿病组大鼠额叶脑皮质神经细胞中磷酸化-ERK1/2以及大鼠额叶脑皮质、灰质核团神经细胞中的磷酸化-Elk-1的阳性率均高于同期对照组以及第3天、第2周糖尿病组大鼠(P<0.05),糖尿病组大鼠第8周额叶脑皮质核团神经细胞中磷酸化ERK1/2和磷酸化Elk-1表达的阳性率高于第4周(P<0.05).制模后第2、4、8周的糖尿病组大鼠的额叶脑灰质神经细胞中磷酸化ERK1/2阳性率均高于同期对照组和制模后第3天(P<0.05),且随着制模时间的延长,磷酸化ERK1/2阳性率逐渐增高(P<0.05).结论 糖尿病大鼠在制模后第4、8周额叶神经细胞中存在ERK1/2信号转导通路的异常激活.