Inhibitory effects of chiral 3-n-butylphthalide on inflammation following focal ischemic brain injury in rats^1  

手性丁基苯酞对大鼠局灶性脑缺血后炎症的抑制作用(英文)

作　　者：徐皓亮[1] 冯亦璞[1] 

机构地区：[1]中国协和医科大学中国医学科学院药物研究所

出　　处：《Acta Pharmacologica Sinica》2000年第5期51-56,共6页中国药理学报（英文版）

基　　金：Project supported by the State Science and Technology Commission Grant (№ 94-ZD-01);by the National Natural Science Founda-tion of China (№ 29790122).

摘　　要：AIM: To evaluate the degree of neutrophil infiltration into ischemic tissue after transient focal cerebral ischemia, and to examine the effects of chiral 3-n-butylphthalide (NBP) on this inflammatory process. METHODS: After a 24-h reperfusion following transient cerebral ischemia, two different techniques, histologic analysis and modified myeloperoxidase (MPO)-quantification method, were utilized to identify the infiltration of neutrophils into cerebral tissue following ischemia. The expression of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α(TNF-α) in the ischemic zone were observed by immunohistochemistry, Western blot, and in situ hybridization techniques. RESULTS: In cerebral cortex area perfused by middle cerebral artery (MCA), MPO activity was greatly increased after 24 h of reperfusion in the vehicle group, and it correlated well with the infiltration of neutrophils. Administration of dl-, d-, and l-NBP (20 mg·kg-1) partially inhibited both the increase in MPO activity and the appearance of neutrophils in ischemia-reperfusion sites. Up-regulation of ICAM-1 was also observed on the microvessel endothelium in the ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression, and decreased the number of TNF-α blue purple-positive neurons induced by ischemia-reperfusion injury. CONCLUSION:The results indicate that the increase in neutrophils infiltration into the in-farct site implicated postischemic brain injury, and NBP was effective in protecting the ischemic sites following ischemic insult.目的:观察脑缺血后中性粒细胞浸润与脑损伤的关系,并研究了消旋和光活丁基苯酞对脑缺血后炎症损伤的影响。方法:利用组织化学及髓过氧化物酶定量测定法,观察了中性粒细胞浸润程度。同时,通过免疫组织化学方法及Western blot,观察了脑缺血再灌后,缺血区细胞间粘附分子-1的表达;并用原位杂交技术研究了缺血区肿瘤坏死因子(TNF-α)mRNA表达的变化。结果:dl-,d-和l-NBP均能明显降低缺血再灌注时脑损伤区的中性粒细胞数目及MPO酶的活性,并可以抑制缺血区ICAM-1及TNF-α表达的升高。结论:中性粒细胞浸润是局灶性脑缺血后损伤的重要原因之一,NBP可以通过抑制脑缺血后炎症的发生而产生脑保护作用。

关 键 词：cerebral ischemia INFLAMMATION 3-N-BUTYLPHTHALIDE NEUTROPHILS intercellular adhesion molecule-1 tumor necrosis factor Western blotting in situ hybridization 

分 类 号：R96[医药卫生—药理学]