大鼠脑缺血再灌注损伤后脑组织MMP-9的表达及神经调节素的干预作用  

Expression of MMP-9 and regulation of neuregulin on the brain of rats following ischemia/reperfusion

作　　者：王海萍[1,2] 李增伟 迟兆富[1] 

机构地区：[1]山东大学齐鲁医院神经内科,济南250012 [2]青岛大学医学院附属医院脑血管病内科,山东青岛266003 [3]山东省寿光市第四人民医院神经内科,山东寿光262735

出　　处：《山东大学学报（医学版）》2009年第5期78-82,共5页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金资助项目(Y2004C04,Z2007D05);青岛市科技局基金资助项目(06-2-2-4-NSH-1)

摘　　要：目的观察大鼠脑缺血再灌注损伤基质金属蛋白酶(MMP-9)表达及神经调节素-1β(NRG-1β)的干预作用。方法取成年健康雄性Wister大鼠100只,应用线拴法经颈外-颈内动脉插线建立大脑中动脉闭塞再灌注(MCAO/R)动物模型,经颈内动脉单剂量注射1.5%NRG-1β5μL干预治疗。采用免疫组化、免疫荧光、免疫印迹法,观察脑组织MMP-9表达。结果脑缺血再灌注损伤可诱导脑组织MMP-9表达。随着缺血缺氧时间的延长,对照组MMP-9蛋白的表达逐渐增加,阳性细胞形态大小不一,分布于脑组织各区。NRG-1β治疗可降低MMP-9的表达水平,与对照组相应脑区相比,差异显著(P<0.01)。结论MMP-9参与脑缺血再灌注损伤后的炎症反应过程。NRG-1β可能通过调节脑组织中MMP-9的活性,干扰脑缺血再灌注损伤后炎症的发生发展过程,改善神经元的生存环境,延迟神经元损伤的时间和程度,进而对缺血性脑损伤具有积极的保护作用。Objective To explore expression of matrix metaUoproteinase-9 （MMP-9） and effect of neuregulin-1β （NRG-1β） on brain tissues of rats following cerebral ischemia/reperfusion. Methods Animal models of middle cerebral artery occlusion/reperfusion （MCAO/R） were established by a filament method in the left external-internal carotid artery in 100adult healthy male Wister rats. Rats in the treatment group were injected with 1.5%NRG-1β 5 μL in the internal carotid artery（ICA）. Expression of MMP-9 was determined by immunohistochemical and immamofluorescent staining and western-blotting assay. Results Hypoxia and ischemia can cause expression of MMP-9. With the prolongation of the ischemic time, an increased expression of MMP-9 was obtained in the control group. Expression of MMP-9 was decreased in the NRG-1β treatment group compared with the control group at the same time point and the corresponding region（ P 〈 0.01）, Conclusion MMP-9 might contribute to inflammatory reaction after ischemia-reperfusion cerebral insult by different methods. NRG-1β might regulate the activation of MMP-9, disturb the development of inflammatory reaction, improve the micro-environment of neuron survival, delay the course and degree of the neuron by various methods, and further play a neuro-protective role in ischemia cerebral insult.

关 键 词：神经调节素 缺氧缺血 脑 再灌注损伤 明胶酶B 荧光抗体技术 免疫印迹法 大鼠 WISTAR 

分 类 号：R739.41[医药卫生—肿瘤]