摘要
目的:观察6 mg.kg-1阿司匹林对大鼠脑缺血-再灌注损伤的保护作用及机制。方法:线栓法制作局部脑缺血2 h、再灌24 h模型,观察6 mg.kg-1阿司匹林对脑损伤面积、正常锥体神经元密度、脑病理学改变及血前列环素(PGI2)/血栓素(TXA2)、脑组织髓化过氧化物酶(MPO)、丙二醛(MDA)、ATP含量、凋亡细胞数目及Bcl-2和Bax基因蛋白的影响。结果:6 mg.kg-1剂量阿司匹林明显缩小再灌注引起的脑损伤范围,改善脑病理形态,抑制再灌注引起的正常神经元的丢失和凋亡细胞数目,提高Bcl-2/Bax,提高血PGI2/TXA2。但对脑组织MPO、MDA及ATP无明显影响。结论:6 mg.kg-1阿司匹林对脑缺血-再灌注损伤有明显保护作用,其机制可能与提高PGI2/TXA2、抑制细胞凋亡及提高Bcl-2/Bax有关。
AIM： To investigate the protective effects and the mechanism of low dose aspirin on focal cerebral ischemia-repeffusion rats. METHODS： Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 2 h, and then repeffused for 24 h. 6 mg· kg^-1 dose of aspirin was intragastric administered at reperfusion 0 and 6 h. The brain injuried area, the neuronal density, the numbers of apoptotic cells and the ratio of Bcl-2 protein and Bax protein from occluded brain were estimated. The ratio of prostacyclin （PGI2） and thromboxane （TXA2 ） in plasma, the contents of malondialdehyde （MDA）, adenosion 5＇-triphosphate （ATP） and myeloperoxidase （MPO） in brain tissue from the occluded side were assayed. Apoptosis was measured in parafrin sections with TUNEL method. Bcl-2 and Bax were detected by immunohistochemical staining method. Adjacent sections were stained with hematoxylin and eosin, and neuronal density subfield was counted. The contents of PGI2 and TXA2 in plasma were measured by ^125I radioinununoassay method. The content of MDA and MPO in brain tissue was determined by biochemical method. The content of ATP in brain tissue was separated by capillary electrophoresis. RESULTS： The injuried area of brain occluded side was dramatically reduced after 6 mg·kg^-1 dose of aspirin was intragastric administrated. Most of neurons in the injuried regions survived ischemia-reperfusion result when 6 mg· kg^-1 dose of aspirin was given, where as most of vehicle group neurons were lost without aspirin treatment. The numbers of apoptotic cells were dramatically reduced by 6 mg· kg^-1 dose of aspirin. The ratio of Bcl-2 and Bax was increased by aspirin. The ratio of PGI2/TXA2 in plasma was increased by aspirin. In brain tissue of occluded side, no significant change between 6 mg· kg^-1 and vehicle groups in MDA content, ATP level, and MPO content were discovered. CONCLUSION： The neuroprotective effects of low dose of aspirin on focal cerebral ischemia-reperfusion rat
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第6期659-664,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
