糖尿病大鼠脑缺血再灌注后细胞外信号调节激酶1／2表达与海马CA4区神经元凋亡  

Expression of extracellular signal-regulated kinase 1/2 and neuronal apoptosis in hippocampal CA4 region after cerebral ischemia-reperfusion in diabetic rats

作　　者：马轶[1] 景丽[1] 郭凤英[1] 张建中[1] 

机构地区：[1]宁夏医科大学基础医学院病理学教研室,银川750004

出　　处：《国际脑血管病杂志》2009年第8期573-576,共4页International Journal of Cerebrovascular Diseases

基　　金：国家自然科学基金（30560044）;宁夏高等学校科研基金（2005055）;宁夏医科大学面上项目（2006009）

摘　　要：目的探讨糖尿病大鼠脑缺血再灌注后神经元细胞外信号调节激酶（extracellular signal—regulated kinase，ERK）1／2表达及其意义。方法72只健康成年sD大鼠随机分假手术组、正常血糖脑缺血组和糖尿病脑缺血组，每组根据缺血再灌注不同时点分为缺血15min再灌注1h,3h,6h亚组，每个亚组6只。采用链脲佐菌素诱导糖尿病，双血管闭塞联合放血法建立糖尿病大鼠全脑缺血模型。应用IUNEL和免疫组化方法观察海马CA4区神经元凋亡和磷酸化ERK1／2表达。结果糖尿病脑缺血组在缺血15min、再灌注1h、3h、6h各时间点海马CA4区神经元凋亡发生率均明显高于正常血糖脑缺血组（P〈0．05）；糖尿病脑缺血组在各时间点磷酸化ERK1／2均有较高表达，在再灌注1h和3h时均明显高于正常血糖组（P〈0．01）。结论ERK1／2可能参与了糖尿病加重脑缺血再灌注后神经元损伤的机制。Objective To investigate the expression of neuronal extracellular signalregulated kinase 1/2 （ERK1/2） and its significance after cerebral ischemia reperfusion in diabetic rats. Methods Seventy-two healthy adult SD rats were randomly divided into shamoperation, normal glucose with cerebral ischemia and diabetes with cerebral ischemia groups. Each group was redivided into ischemia 15 minutes and reperfusion 1, 3 and 6 h subgroups according to the different time points of ischemia reperfusion （n = 6 in each subgroup）. Streptozocin was used to induce diabetes, and a global cerebral ischemia model of diabetic rat was established by the bilateral vascular occlusion combining with bloodletting. TUNEL and immunohistochemistry were used to observe neuronal apoptosis and the expression of the phosphorylation of ERK1/2 in hippocampal CA4 region. Results The incidences of neuronal apoptosis in hippocampal CA4 region for ischemia 15 minutes and reperfusion 1,3 and 6 h in the diabetes with cerebral ischemia group were significantly higher than those in the normal glucose with cerebral ischemia group （P 〈 0.05）; the expressions of the phosphorylation of ERK1/2 at all time points in the diabetes with cerebral ischemia group were higher, and reperfusion 1 and 3 h were significantly higher than those in the normal glucose with cerebral ischemia group （P 〈 0.01 ）. Conclusions ERK1/2 might involved in the mechanism of neuronal injury after diabetes aggravating cerebral ischemia-reperfusion.

关 键 词：丝裂原活化蛋白激酶1 脑缺血 再灌注损伤 细胞凋亡 糖尿病 大鼠 

分 类 号：R285.5[医药卫生—中药学]