糖尿病合并缺血性脑梗死后脑组织RECK表达及其与MMP-9关系的实验研究

摘要

Objective To explore the involvement of reversion inducing cysteine rich protein with Kazal motifs (RECK) and matrix metalloproteinase-9 (MMP-9) in diabetic cerebral ischemia.Methods One hundred and ten wistar rats were randomly divided into simulate operation group,cerebral ischemia group(CI group) and diabetic cerebral ischemia group(DM + CI group).The diabetic rat models were established by high fat,saccharose diets and streptozotion injections.The middle cerebral artery occlusion models were made by improved zealong's method.The expressions of RECK and MMP-9 were examined by immunohistochemistry staining.Results RECK and MMP-9 located mainly in the cytoplasm of neurons,neuroglia cells and etc in the ischemic penumbra zones.RECK distribution significantly decreased in both ischemic groups (P ＜ 0.01).At every reperfusion point,less RECK(+)cells in DM + CI group were detected than CI group (P ＜0.05).RECK decreased at 3 hours,minimum at 24 hours,then gradually increased after 3 days in both ischemic groups.MMP-9 significantly increased in both ischemic groups (P ＜ 0.05).MMP-9 increased significantly more than that in CI group (P ＜0.05),peaked at 24 hours.Negative correlation of MMP-9 in DM + CI group and RECK were detected at 3 hours to 24 hours after reperfusion.Conclusion The reduction of RECK possibly contribute to the increase of MMP-9,which may be one reason for infarction injuries and terrible results in cerebral ischemia of diabetic patients.%目的 观察RECK、基质金属蛋白酶-9(MMP-9)在糖尿病合并脑梗死(CI)后脑组织损伤中的作用.方法 将110只Wister大鼠随机分成假手术组、单纯脑梗死组(CI组)和糖尿病合并脑梗死DM组+CI组.采用高糖高脂饮食及腹腔注射小剂量链脲霉素法制作糖尿病大鼠模型,线栓法实现大脑中动脉缺血再灌注模型,免疫组化法检测脑组织RECK、MMP-9表达.结果 RECK和MMP-9主要表达于缺血半暗带神经元、神经胶质细胞等处;CI组、DM+CI组RECK较假手术组表达明显减少(P＜0.05或P ＜0.01),且DM+CI组较CI组明显减少(P＜0.05).DM+CI组RECK于再灌注3h表达开始降低,24 h达波谷,后逐渐增加.CI组、DM+CI组MMP-9表达较假手术组明显增加(P＜0.05),且DM+CI组较CI组明显增加(P＜0.05);DM+CI组MMP-9于再灌注3h开始升高,24h达波峰,7d后渐下降;梗死后脑内MMP-9与RECK蛋白表达呈直线负相关.结论 糖尿病合并脑梗死大鼠脑内RECK表达减少与MMP-9表达上升相关,考虑两者参与糖尿病合并脑梗死后脑缺血改变及功能恢复.