摘要
目的观察局灶性脑缺血预处理(CIP)对Toll样受体4(TLR4)及胶质原纤维酸性蛋白(GFAP)表达的影响,探讨TLR4介导的炎性信号通路及星形胶质细胞活化在诱导脑缺血耐受(BIT)发生中的作用。方法第1次脑缺血20min作为预处理,72h后行持续2h的第2次局灶性脑缺血。45只SD雄性大鼠随机分为脑缺血预处理(CIP)组、大脑中动脉阻塞(MCAO)组、假手术(sham)组。MCAO组第1次脑缺血以假手术代替,假手术组两次均为假手术。第2次脑缺血后每组又分再灌注6、24、72h等3个时间段。光学显微镜下观察脑组织病理改变,免疫组织化学染色和图像分析评价各组TLR4及GFAP的表达。结果 CIP组TLR4阳性细胞数明显低于同时间段的MCAO组,而GFAP阳性细胞数则均高于同时间段的MCAO组(P<0.05)。TLR4、GFAP在CIP组及MCAO组的表达高峰均分别出现于再灌注后6、72h。结论短暂的CIP可能通过抑制TLR4炎症信号通路,明显激活反应性星形胶质细胞,从而诱导脑缺血耐受的发生。
Objective To investigate the expressions of TLR4 and GFAP in the ischemic tolerance induced by focal cerebral ischemic preconditioning and discuss the role of TLR4 inflammatory signaling pathway and activated astrocytes in brain ischemic tolerance（BIT）. Methods 20 rain middle cerebral artery occlusion（MCAO） by intraluminal filament was used as cerebral ischemic preconditioning（CIP）. The second MCAO was induced for 2 b and operated at 72 h after CIP. 45 male SD rats were randomly divided into 3 groups（15 in each group） ：sham operation group received twice sham surgery only,and the other 2 groups received the sec ond MCAO followed by 6 h,24 h,72 h reperfusion with CIP or sham surgery respectively. At the end of reperfusion the expressions of TLR4 and GFAP were detected by immunohistochemistry method in each group. Results The rate of TLR4 positive cells in the brain of CIP group was significantly lower than that of MCAO group at every time point tested（P〈0.05）. On the contrary, the number of GFAP labeled cells in CIP group was more than that of MCAO group. The expressions of TLR4 and GFAP peaked at 6 b and 72 b respectively both in CIP group and MCAO group. Conclusion These findings support the transient CIP could decrease the expression of TLR4 and restrain the following inflammation, furthermore,CIP might facilitate the proliferation and activation of astrocytes around infarct area to induce brain ischemic tolerance.
出处
《重庆医学》
CAS
CSCD
北大核心
2012年第29期3076-3078,I0002,共4页
Chongqing medicine
基金
四川省教育厅青年基金资助项目(2009ZB014)
