重组人谷氧还蛋白1对小鼠脑缺血/再灌注损伤的保护作用  

Protective effect of recombinant human glutaredoxin-1 against the cerebral ischemia-reperfusion injury in mice

作　　者：吴莉芳[1] 刘莹莹[1] 房绍红[1] 周宏博[1] 邹朝霞[1] 杨歌德[1] 任亚坤[2] 

机构地区：[1]哈尔滨医科大学生物化学与分子生物学教研室,黑龙江哈尔滨150086 [2]齐齐哈尔市卫生学校生物化学教研室,黑龙江齐齐哈尔161005

出　　处：《中国药理学通报》2007年第5期641-644,共4页Chinese Pharmacological Bulletin

基　　金：黑龙江省自然科学基金(No2004-05);黑龙江省博士后启动基金;黑龙江省卫生厅基金(No2006-274)资助项目

摘　　要：目的探讨重组人谷氧还蛋白1(rhGrx1)对小鼠局灶性脑缺血/再灌注损伤的保护作用及机制。方法线栓法制备小鼠脑缺血/再灌注模型,病理形态学方法证实模型建立成功。小鼠尾静脉注射rhGrx1(5mg·kg-1和10mg·kg-1)后,观察脑组织中乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)及蛋白质羰基含量的变化,Western blot检测小鼠脑组织中p38MAPK表达水平的变化。结果HE染色证实模型建立成功且提示rhGrx1可改善缺血/再灌注损伤所致的小鼠脑组织病理形态学变化;rhGrx1能增加小鼠脑组织LDH、SOD活性、降低蛋白质羰基的含量。与假手术组小鼠相比,缺血和再灌注时脑组织p38MAPK蛋白表达量明显增加,注射rhGrx1后p38MAPK蛋白表达被抑制。结论rh-Grx1对局灶性脑缺血/再灌注损伤小鼠有一定保护作用,其机制可能与抑制p38MAPK蛋白表达相关。Aim To explore the effects of recombinant human Glutaredoxin-1 on the focal cerebral ischemicreperfusion damage in mice and its possible mechanism. Methods The model of cerebral isehemiareperfusion in mice was established with the suture-occluded method, and identified to be successful by pathohistologieal method. The levels of Lactate dehydrogenase （ LDH ）, superoxide dismutase （ SOD ） and protein earbonyl content in brain tissue were measured after intravenously administering rhGrxl at the doses of 5 and 10 mg·kg^-1 by caudal vein. The protein levels of p38MAPK in brain tissue were detected by Western blot. Results The murine model was confirmed by HE stain, and the pathological changes suggested that rhGrxl could relieve the injury of ischemia-reperfusion. The rhGrxl could increase the levels of LDH ,SOD and reduce protein carbonyl contents. Compared with mice in sham operation group, the expression level of p38MAPK were increased significantly during the ischemic period and reperfusion, but could be inhibited by injecting rhGrx1. Conclusions The rhGrx1 could protect mice from the injury following ischemia-reperfusion and the mechanism may be related to the inhibition of p38MAPK.

关 键 词：谷氧还蛋白 脑缺血/再灌注损伤 LDH SOD 蛋白质羰基含量 P38MAPK 

分 类 号：R-332[医药卫生] R322.81