乌司他丁对大鼠脑缺血再灌注时代谢型谷氨酸受体Ⅱ表达的影响  

Effect of ulinastatin on expression of metabotropic glutamate receptorⅡduring cerebral ischemia-reperfusion in rats

作　　者：豆立冬[1] 王婕[1] 王开伟[1] 林洪启[1] Dou Lidong;Wang Jie;Wang Kaiwei;Lin Hongqi(Department of Anesthesiology,Henan Provincial People′s Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院麻醉科,郑州450003

出　　处：《中华麻醉学杂志》2019年第3期296-299,共4页Chinese Journal of Anesthesiology

基　　金：河南省医学科技攻关计划(201503178);河南省医学教育研究项目(Wjlx2015068).

摘　　要：目的评价乌司他丁对大鼠脑缺血再灌注时代谢型谷氨酸受体Ⅱ(mGluRⅡ)表达的影响.方法雄性SD大鼠48只,6~8周龄,体重230~280g,采用随机数字表法分为3组(n=16):假手术组(S组)、脑缺血再灌注组(I∕R组)和乌司他丁组(U组).采用线栓法阻断大鼠右侧大脑中动脉2h恢复灌注,制备脑缺血再灌注损伤模型.U组于再灌注即刻尾静脉注射乌司他丁10万U∕kg.于再灌注24h后行神经功能缺陷评分,然后处死大鼠,取脑组织,采用TTC染色法观察脑梗死情况,计算脑梗死体积百分比,采用Westernblot法测定脑缺血半暗带区IκB-α的表达,采用免疫荧光染色法测定脑缺血半暗带区mGluRⅡ的表达.结果与S组比较,I∕R组和U组神经功能缺陷评分和脑梗死体积百分比升高,脑缺血半暗带区mGluRⅡ表达上调,IκB-α表达下调(P<0.05).与I∕R组比较,U组神经功能缺陷评分和脑梗死体积百分比降低,脑缺血半暗带区mGluRⅡ表达下调,IκB-α表达上调(P<0.05).结论乌司他丁减轻大鼠脑缺血再灌注损伤的机制可能与抑制脑缺血半暗带区mGluRⅡ的表达有关.Objective To evaluate the effect of ulinastatin on the expression of metabotropic glutamate receptorⅡ(mGluRⅡ)during cerebral ischemia-reperfusion(I/R)in rats.Methods Forty-eight male Sprague-Dawley rats,aged 6-8 weeks,weighing 230-280 g,were divided into 3 groups(n=16 each)by a random number table method:sham operation group(S group),cerebral I/R group(I/R group)and ulinastatin group(U group).The model of cerebral I/R injury was established by occluding the right middle cerebral artery using a nylon thread with a rounded tip inserted into internal carotid artery and advanced cranially until resistance was met.Middle cerebral artery occlusion was maintained for 2 h followed by 24-h reperfusion.Ulinastatin 100 000 U/kg was injected via the tail vein immediately after onset of reperfusion in group U.The neurological deficit score(NDS)was assessed after 24 h of reperfusion.The rats were then sacrificed,and brain tissues were obtained for determination of brain infarction(by TTC staining),expression of IκB-αin cerebral ischemic penumbra(by Western blot)and expression of mGluRⅡin cerebral ischemic penumbra(by immunofluorescent staining).The percentage of cerebral infarct volume was calculated.Results Compared with S group,the NDS and percentage of cerebral infarct volume were significantly increased,the expression of mGluRⅡin cerebral ischemic penumbra was up-regulated,and the expression of IκB-αin cerebral ischemic penumbra was down-regulated in I/R and U groups(P<0.05).Compared with I/R group,the NDS and percentage of cerebral infarct volume were significantly decreased,the expression of mGluRⅡin cerebral ischemic penumbra was down-regulated,and the expression of IκB-αin cerebral ischemic penumbra was up-regulated in U group(P<0.05).Conclusion The mechanism by which ulinastatin mitigates cerebral I/R injury may be related to inhibiting the expression of mGluRⅡin cerebral ischemic penumbra of rats.

关 键 词：胰蛋白酶抑制剂 再灌注损伤 脑 受体 谷氨酸 

分 类 号：R965[医药卫生—药理学]