细胞外信号调节激酶在高血糖加重脑缺血性损伤中的作用.DOCVIP

临床医学论文-细胞外信号调节激酶在高血糖加重脑缺血性损伤中的作用 【摘要】? 目的 探讨ERK1/2在高血糖加重大鼠脑缺血再灌注损伤中的作用。方法 采用双侧颈总动脉管阻断加低血压法建立脑缺血再灌注模型，大鼠缺血前30min注射25％葡萄糖，使之处于高血糖状态。两侧颈总动脉结扎并放血，使血压下降到45～50mmHg。脑缺血30min后再灌注(解除颈总动脉结扎同时回输血液)，分别观察再灌注后30min、1h、3h、6h。另设正常血糖组和对照组，用免疫组化和Western blot比较3组大鼠ERK1/2的表达状态和脑组织病理改变。结果 正常血糖组和高血糖组大鼠，再灌注后0～1h，海马CA1区未见明显的ERK1/2表达。而在纹状皮质和海马CA3区，ERK1/2的表达有明显的区别。正常血糖组大鼠在再灌后30min，可见ERK1/2轻度升高，高血糖组大鼠再灌注后30min，ERK1/2升高。ERK1/2在再灌注1h达到高峰并且持续到再灌注3、6h，高于正常血糖组(P＜0.05)。用Western blot方法检测皮质和海马的ERK1/2含量，正常血糖组在缺血再灌注30min、1h、3h、6h ERK1/2含量逐渐升高，而高血糖组又高于正常血糖组(P＜0.05)。结论 高血糖可加重脑缺血再灌注损伤，其机制可能与激活ERK1/2有关。 【关键词】? 细胞外信号调节激酶；高血糖；脑缺血；再灌注损伤 　　Abstract: Objective? To investigate whether ERK1/2 was involved in mediating hyperglycemia-exaggerated cerebral ischemic damage. Methods? Using bilateral carotid artery ligation upon the blood flow method，the model of cerebral ischemic reperfusion was established in rats. 25% glucose was injected at 30 min before the induction of ischemia to yield a glucose concentration more than 15mM. Cerebral ischemia was induced by bilateral clamping of the carotid artery plus hypotension to 45-50 mmHg by withdrawing and infusing blood. At the end of 30-min ischemia, the clamps were removed and the blood reinfused. The animals were anesthetized to allow collection of brains after 30 min, 1, 3 or 6h of reperfusion. In addition, normoglycemic group and control group were set. Then using immunohistochemistry and western blot compared with expression level of ERK1/2 and the pathological change among the rats in three groups. Results?No obvious expression of ERK was abserved in the hippocampal CA1 sector in either normoglycemic or hyperglycemic rats after 0h of reperfusion. In contrast there was a clear difference for the expression of ERK1/2 in the hippocampal CA3 sector and In the stride cortex area between normoglycemic and hyperglycemic rats. The number of positive cell in hyperglycemic group is significantly higher than that in the normoglycemic group after 30 min, 1, 3, 6 hours reperf