脑缺血再灌注的炎症损伤分子机制及吲哚美辛的保护作用  

Effects of indomethacin on inflammatory process induced by focal cerebral ischemia-reperfusion in rats and its mechanism

作　　者：刘皖生[1] 唐乙[2] 郑余银[1] 宋少华[2] 卢君艳[1] 刘芳[2] 田野苹[2] 

机构地区：[1]温州医学院第二附属医院神经内科,浙江温州325027 [2]第二军医大学免疫学教研室

出　　处：《解放军医学杂志》2007年第10期1051-1053,共3页Medical Journal of Chinese People's Liberation Army

基　　金：温州市科技计划基金资助项目(Y2004A068)

摘　　要：目的研究大鼠局灶性脑缺血再灌注炎症损伤的分子机制，并观察吲哚美辛对脑缺血再灌注炎症损伤的保护作用。方法36只雄性SD大鼠随机分为假手术组，模型组，吲哚美辛3、6、9mg/kg组，每组6-8只。应用线栓法制作大鼠局灶性脑缺血再灌注模型，缺血2h再灌注24h后处死动物，以TTC染色法测定脑梗死范围和神经功能缺损情况，并分别采用ELISA、Western blot法检测脑组织中IL-8、IL-1β、TNF-α、髓过氧化物酶（MPO）含量以及细胞间黏附分子1（ICAM-1）、E选择素（E-selectin）的表达。结果吲哚美辛能明显减小模型大鼠的脑梗死范围，减轻神经损伤症状；预先给予吲哚美辛（6、9mg/kg）可降低脑组织中MPO活性及IL-8、IL-1β、TNF-α的水平，并减少ICAM-1、E-selectin的表达（P〈0.05或0.01）。结论吲哚美辛可通过抑制脑缺血再灌注过程中炎症介质的表达和释放，降低脑缺血再灌注所致的炎症损伤。Objective Cerebral ischernia would rapidly initiate structural and functional damages in brain, including blood-brain barrier disruption, inflammation, and angiogenesis. The purpose of present study is to investigate the effects of indomethacin, an agent that inhibits cyclooxygenase, on the inflammatory reaction after cerebral ischemia-reperfusion in transient middle cerebral artery occlusion （MCAO）rats and its possible mechanism. Methods Adult male SD rats weighed 250-250g were subjected to either sham surgery or middle cerebral artery occlusion （MCAO） for 2h of brain ischemia and 24h reperfusion. After 24h of reperfusion,the size of cerebral infarction and the neurological deficit were determined by the method of TTC （2,3,5-Triphenyltetrazolium Chloride） staining and Longa＇s score analysis. The contents of IL-8, IL-1β, TNF-α and MPO in brain tissue were assayed by ELISA. The expressions of ICAM-1 ande E-selectin were evaluated with Western-blot. Results It was observed that indomethacin （6 or 9mg/kg i. p pretreatment for 5d, once a day） significantly reduced cerebral infarct volume and ameliorated the neurological deficit （P〈0. 05 or P〈0. 01 vs vehicle group）. Pretreatment with indomethacin （6mg/kg or 9mg/kg） for 5 days, the content of IL-8, IL-1β, TNF-α and MPO activity as well as the protein expressions of ICAM-1, E-selectin in brain tissue were significantly decreased as compared with the vehicle group （P〈0. 05 or P〈0. 01）. Conclusion Indomethacin have protective effects on cerebral injury through inhibiting the expression and releasing of the inflammatory mediators after cerebral ischemia-reperfusion, which may be an important mechanism for its resisting ischemic and reperfusion injury.

关 键 词：白细胞介素1 白细胞介素8 肿瘤坏死因子 胞间黏附分子1 E选择素 吲哚美辛 脑缺血 

分 类 号：R743.33[医药卫生—神经病学与精神病学]