缺血后处理局灶性脑缺血再灌注模型大鼠相关通路以及白细胞介素8的表达  

Effects of ischemic postconditioning on related pathways and interleukin 8 expression in rat models of focal cerebral ischemia/reperfusion

作　　者：李志行[1] 吕敬雷[2] 陈萍[1] 赵仁亮[2] 

机构地区：[1]青岛大学医学院,山东省青岛市266000 [2]青岛大学附属医院神经内科,山东省青岛市266003

出　　处：《中国组织工程研究》2015年第49期7938-7944,共7页Chinese Journal of Tissue Engineering Research

基　　金：青岛市科技局立项课题(14-2-3-14-nsh)~~

摘　　要：背景:缺血后处理能够激发内源性保护作用,抑制缺血再灌注后的炎症反应,但具体机制目前尚不明确。目的:观察缺血后处理对局灶性脑缺血再灌注大鼠Toll样受体4-核因子κB信号转导通路以及白细胞介素8表达的影响,进一步阐述缺血后处理的神经保护机制。方法:将110只大鼠随机分为假手术组10只、模型组和缺血后处理组各50只,将大鼠按照Zea-Longa法建立局灶性脑缺血再灌注模型,再进行缺血后处理,即大脑中动脉闭塞2 h后进行3个循环的再灌注15 s/缺血15 s,设模型组和假手术组作对照。对各组进行神经行为学评分,TTC染色测定脑梗死体积,免疫组织化学法检测脑组织Toll样受体4、核因子кB和白细胞介素8蛋白表达,原位杂交法检测其mR NA表达。结果与结论:模型组、缺血后处理组大鼠都出现神经行为学缺失及缺血侧大脑半球梗死。再灌注6,12,24,48,72 h,与模型组相比,缺血后处理组大鼠神经行为学评分显著改善(P<0.05)、脑梗死体积明显减少(P<0.05)。模型组和缺血后处理组Toll样受体4、核因子кB、白细胞介素8蛋白和mR NA表达于再灌注6 h时已升高,24 h达峰值。再灌注6,12,24,48,72 h,与模型组各对应时间点亚组比较,缺血后处理组上述各因子表达均显著降低(P<0.05)。结果证实,缺血后处理可抑制缺血再灌注引起的炎症反应,通过抑制Toll样受体4-核因子κB信号转导通路和下调白细胞介素8的表达,以此发挥神经保护作用。BACKGROUND： Ischemic postconditioning may motivate endogenous protective effect and inhibit inflammatory response after ischemia/reperfusion, but the specific mechanism is still unclear.OBJECTIVE： To investigate the effects of ischemic postconditioning on Toll-like receptor 4/nuclear factor кB signaling transduction pathway and interleukin 8 expression in rat models of focal cerebral ischemia/reperfusion, and further illustrate the neuroprotective mechanism of ischemic postconditioning. METHODS： One hundred and ten rats were randomly divided into sham group（n=10）, model group（n=50） and ischemic postconditioning group（n=50）. Focal cerebral ischemia/reperfusion rat models were established according to Zea-Longa method, and then subjected to ischemic postconditioning, i.e., middle cerebral artery occlusion for 2 hours followed by 3 cycles of 15-second reperfusion/15-second ischemia. Model group and sham group were set for comparison. In each group, rat neurobehavioral deficit scores were evaluated, and rat infarct volume was measured with TTC staining. The expression of Toll-like receptor 4, nuclear factor кB and interleukin 8 protein in brain tissue was detected by immunohistochemistry. Their m RNA expression was detected by in situ hybridization.RESULTS AND CONCLUSION： Rats in the model and ischemic postconditioning groups all presented neurobehavioral deficits and cerebral hemisphere infarction on the ischemic side. At 6, 12, 24, 48 and 72 hours after reperfusion, the neurobehavioral deficit scores were significantly decreased in the ischemic postconditioning group compared with that in the model group（P 〈0.05）. The infarct volume of rats in the ischemic postconditioning group was significantly decreased compared with that in the model group（P 〈0.05）. The expression of Toll-like receptor 4, nuclear factor кB and interleukin 8 protein and m RNA was increased at 6 hours after reperfusion and reached the peak at 24 hours after reperfusion. At 6, 12, 24, 48 and 72 hours after reperf

关 键 词：组织工程 脑缺血 模型 动物 白细胞介素8 实验动物模型 脑及脊髓损伤动物模型 再灌注损伤 缺血后处理 炎症反应 神经保护 动物模型 SD大鼠 Toll样受体4 核因子КB 

分 类 号：R318[医药卫生—生物医学工程]