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中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (6): 659-664.

• 研究原著 • 上一篇    下一篇

小剂量阿司匹林对脑缺血-再灌注损伤的保护作用及机制

邱丽颖, 余涓1, 周宇1, 陈崇宏1   

  1. 江南大学医学系, 无锡 214000, 江苏;
    1福建医科大学药理教研室, 福州 350004, 福建
  • 收稿日期:2006-03-20 修回日期:2006-04-10 出版日期:2006-06-26 发布日期:2020-12-04
  • 作者简介:邱丽颖,女,博士,教授,硕士生导师,研究方向:心脑血管病。Tel:0510-85715660 E-mail:qiulydoc@sina.com

Protective effects and mechanism of low dose aspirin on focal cerebral ischemia-reperfusion rats

QIU Li-ying, YU Juan1, ZHOU Yu1, CHEN Chong-hong1   

  1. Department of Medicine, Southern Yangtze University, Wuxi 214000, Jiangsu, China;
    1Department of Pharmacology, Fujian Medical University, Fuzhou 350004, Fujian, China
  • Received:2006-03-20 Revised:2006-04-10 Online:2006-06-26 Published:2020-12-04

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。

关键词: 阿司匹林, 低剂量, 脑缺血-再灌注损伤, 血前列环素 血栓素, 凋亡, Bcl-2 Bax

Abstract: AIM: To investigate the protective effects and the mechanism of low dose aspirin on focal cerebral ischemia-reperfusion rats.Methods: Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 2 h, and then reperfused 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 paraffin 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 radioimmunoassay 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 rats might be attributed to its effects by increasing the ratio of PGI2/TXA2, inhibiting apoptosis and improving the ratio of Bcl-2 Bax.

Key words: aspirin, low dose, focal cerebral ischemia-reperfusion, prostacyclin thromboxane, apoptosis, Bcl-2 Bax

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