摘要
目的观察阿司匹林对大鼠脑缺血/再灌损伤72h的保护作用及机制。方法线栓法制作局部大脑缺血2h、再灌72h模型,观察60mg·kg-1阿司匹林对脑损伤面积、水肿程度及死亡率的影响;并从抗凋亡、能量代谢及钙调神经磷酸酶活性变化探讨其机制。结果阿司匹林明显缩小再灌注72h引起的脑损伤范围,减轻水肿,降低死亡率,明显降低脑细胞凋亡数目,提高Bcl2/Bax,改善能量代谢,抑制钙调神经磷酸酶的异常升高。结论阿司匹林对脑缺血/再灌损伤72h有明显保护作用,其机制可能与抗凋亡、提高Bcl2/Bax、改善能量代谢及对钙调神经磷酸酶的影响有关。
Aim and mechanism mia-reperfusion bral artery was internal carotid To investigate the protective effects of aspirin against focal cerebral ischein rats. Methods Right middle cereoccluded by inserting a thread thro artery for 2 h, and then reperfused ugh for 72 h. 60 mg · kg^- 1 dose of aspirin was intragastric administrated at 0 h and 6 h after reperfusion. The brain injured area, the mortality, and cerebral edema were estimated. The apoptotic cells of brain tissue were detected by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling （TUNEL） method. Bcl-2 and Bax were detected by immunohistochemical staining method. The activity of calcineurin （CaN） in brain tissue was determined by the inorganic phosphorus method. The content of adenosine 5＇-triphosphate （ATP） in brain tissue was separated by capillary electrophoresis. Results By using of aspirin 60 mg · kg^-1, all indications were dramatically improved. The injured area of brain [from （10.51 ± 1.12）% to （0. 94 ± 0. 08 ） % ] , the cerebral edema of occluded side [from （82.43 ±2. 0）% to （76. 29 ±0. 77）% ], and the mortality [ from 28% to 0% ] were dramatically reduced. In brain tissue of occluded side, 60 mg· kg^-1 aspirin helped to reduce the number of apoptotic cells from （26.43 ±2.0） to （17.53 ±0.44）, increase the ratio of Bcl-2/Bax from （0.61 ±0.05） to （ 1.01±0. 15） , inhibit the activity of CaN from （6.03 ± 1.5 ） to （3.47 ± 0. 96 ） , and improve the ATP level from （ 10. 26 ± 1.02） to （25.65 ±3.45）. Conclusion The neuroprotective effects of aspirin on focal cerebral ischemia-reperfusion injury in rats for 72 h might be attributed to its effects by anti-apoptosis, increasing the ratio of Bcl-2/Bax, inhibiting the activity of CaN, and improving the energy metabolism.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2006年第8期972-976,共5页
Chinese Pharmacological Bulletin
基金
福建省教育厅资助课题(No01A027)
