Bafilomycin A1对脑缺血再灌注损伤小鼠的保护作用及其机制

The Protective Effect and Mechanism of Bafilomycin A1 on Middle Cerebral Ischemia-Reperfusion Injury in Mice

摘要: 目的：探讨洛霉素A(Bafilomycin A1, Baf A1)对脑缺血再灌注损伤(middle cerebral artery occlusion-reperfusion, MCAO/R)小鼠的保护作用及机制。方法：Atg7f/f-Mx1-Cre小鼠15只，随机分为：假手术组(C)、模型组(M)、氟西汀组(M + F)、Baf A1组(M + B)和ATG7敲除组(M + ATG7 KO)。M + B组术前24小时给与脑立体定位注射，M + F组给与氟西汀灌胃连续14 d；其他组均于术前14天开始给予等体积生理盐水。缺血2小时再灌注24 h后，对各组小鼠进行神经行为学评分、脑含水量测定和脑梗死面积检测，Western blotting检测自噬相关蛋白Beclin 1和LC3的表达。结果：与C组相比，M组神经行为评分、脑含水量、脑梗死面积、自噬相关蛋白Beclin 1和LC3的表达显著增加，M + F组、M + B组和M + ATG7 KO组逆转以上结果，差异具有统计学意义。结论：Baf A1通过降低前期和后期细胞自噬水平实现对脑缺血再灌注损伤小鼠的保护作用。

Abstract: Objective: To investigate the protective effect and mechanism of Bafilomycin A1 on middle cerebral ischemia-reperfusion injury in mice. Methods: 15 Atg7f/f-Mx1-Cre mice were randomly divided into sham group (C), model group (M), fluoxetine group (M + F), Baf A1 group (M + B) and ATG7 knockout group (M + ATG7 KO). Group (M + B) was given stereotactic injection 24 hours before operation, Group (M + F) was given intragastric fluoxetine for 14 days, and other groups were given an equal volume of saline 14 days before the operation. After 2 hours of ischemia and 24 hours of reperfusion, the mice in each group were evaluated by neurobehavioral score, cerebral water content and cerebral infarction area. The expression of autophagic related proteins Beclin 1 and LC3 was detected by western blotting. Results: Compared with Group C, the neurobehavioral score, cerebral water content, cerebral infarct size, autophagy associated protein Beclin 1 and LC3 were signifi- cantly increased in group M, and reversed in Group (M + F), Group (M + B) and Group (M + ATG7 KO) and the difference was statistically significant. Conclusion: Baf A1 may protect mice from cerebral ischemia-reperfusion injury by decreasing autophagy levels in the early and late stages.