Objective To investigate the phosphorylation of extracellular signal -regulated kinase (ERK1/2) and ets like gene - 1 ( ELK - 1 ) in meningeal and brain microvascular endothelial cells and smooth muscle cells with diabetic rats and to explore the mechanism of diabetic brain microangiopathy. Methods After modelling 0. 5 weeks, two weeks, four weeks, eight weeks, the spleen central artery angiopathy of Type I diabetic rats , which was induced using intraperitoneal injection of STZ , was respectively observated . The phosphorylation of extracellular signal - regulated kinase( ERK1/2) and ets like gene - 1 ( ELK - 1) in the brain micro-vascular were detected by means of HE staining,and immunohistochemistry techniques. Results p - ERK, p - ELK expressed with different levels in meningeal microvascular endothelial cells, smooth muscle cells, brain microvascular endothelial cells of diabetic groups and normal control group. The up - regulation of phosphorylation ERK1/2 was found in meningeal microvascular endothelial cells, smooth muscle cells, brain microvascular endothelial cells of 8 week,4 week diabetic group. The up - regulation of phosphorylation Elk - 1 expression was found in meningeal and brain microvascular endothelial cells of 8 week, 4 week diabetic group. But there were no significant difference in meningeal microvascular smooth muscle cells between diabetes groups and the normal control groups (P>0.05). Conclusion In 8 week, 4 week diabetic meningeal and brain microvascular exist ERK1 / 2 signal transduction pathway activation.%目的 研究链脲佐菌素诱导的Ⅰ型糖尿病大鼠脑膜、脑实质微血管的病理改变及其中细胞外信号调节激酶ERK1/2及其下游作用底物转录因子Elk-1的磷酸化状态,探讨糖尿病血管的发病机制.方法 应用链脲佐菌素制备Ⅰ型糖尿病大鼠模型,HE染色观察制模后3d和2、4、8周脑膜、脑实质微血管病变,免疫组织化学观察高血糖状态下脑内微血管中p-ERK1/2 及下游作用底物p-ELK1的表达情况.结果 p-ERK1/2、p-ELK1在各时间点正常对照组和糖尿病组大鼠脑膜、脑实质微血管中均有不同程度的表达.p-ERK1/2在糖尿病4、8周组脑膜、脑实质微血管中表达均明显上调;p-ELK1在糖尿病4、8周组脑膜、脑实质微血管内皮细胞中表达均明显的上调(P＜0.05),分别与糖尿病3d、2周组及各期正常对照组比较差异有统计学意义(P＜0.01).糖尿病各组与正常对照组各组脑膜微血管平滑肌细胞中p-ELK1的表达差异无统计学意义(P＞0.05).结论 在糖尿病4、8周组SD大鼠脑内微血管中存在ERK1/2信号转导通路的异常激活.
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