Neuroprotective effect of Bafilomycin A1 on cerebral ischaemia reperfusion injury by regulation AMPK/mTOR/ULK1 signaling pathway in mice
周超瑞 1顾健坤 1陈娜 1李明娟2
扫码查看
点击上方二维码区域，可以放大扫码查看
作者信息
1. 海警医院麻醉科,浙江嘉兴 314000
2. 嘉兴学院医学院,浙江嘉兴 314001
折叠
摘要
目的 探讨巴佛洛霉素A1(BAF-A1)抗小鼠脑缺血再灌注(IR)损伤的腺苷一磷酸活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)/Unc-51样激酶1(ULK1)自噬信号通路的机制.方法 选择SPF级雄性小鼠40只,采用随机数表法分成假手术组(S组)、IR模型组(M组)、BAF-A1组(B组)、BAF-A1+AMPK激动剂组(B+M组),每组10只.以线栓法制备IR模型,以缺血1.5h再灌注24 h后为评价点进行评价.结果 神经功能缺失评分显示,S组无神经功能缺失,B组为(1.47±0.28)分、B+M组为(2.05±0.16)分、M组为(2.45± 0.31)分,B组及B+M组均低于M组(P＜0.05).与M组比较,B组脑梗死体积比率下降(P＜0.05).与S组比较,M组CA1、CA3区有少量的核固缩核裂变、坏死的现象;与M组比较,B组CA1、CA3区的核固缩,核裂变空泡及坏死的症状改善,但B+M组拮抗了这一作用.与S组比较,M组LC3 Ⅱ/Ⅰ、p-AMPK/AMPK蛋白均升高(P＜0.05);与M组比较,B组LC3Ⅱ/Ⅰ、p-AMPK/AMPK蛋白均下降(P＜0.05).与 S 组比较,M 组 p-mTOR/mTOR、Ps757-ULK1/ULK1 蛋白降低;与 M 组比较,B 组 p-mTOR/mTOR、Ps757-ULK1/ULK1 蛋白均升高(P＜0.05).结论 BAF-A1可能通过抑制AMPK/mTOR/ULK1信号通路,抑制小鼠脑海马区的过度自噬,从而发挥神经功能的保护性作用.
Abstract
Objective To investigate the mechanism by which bafilomycin Al(BAF-A1)attenuates cerebral ischemia-reperfusion(IR)injury in mice by regulating autophagy through the adenosine activated protein kinase(AMPK)/mam-malian target of rapamycin(mTOR)/UNC-51 like kinase 1(ULK1)signaling pathway.Methods A total of 40 SPF grade male mice were select for the experiment and randomly divided into sham group(S group),model group(M group),BAF-A1 group(B group)and BAF-A1+AMPK group(B+M group)group.An IR model is prepared using the suture method and evaluated using 1.5 hours of ischaemia followed by 24 hours of reperfusion as the observation point.Results There was no neurological deficit in S group mice,the scores of B Group(1.47±0.28)and Group B+M(2.05±0.16)decreased compared with M Group(2.45±0.31),P＜0.05.Compared with S Group,there was signifi-cant left cerebral ischemia in M Group,B Group and B+M Group,with white infarcted areas visible.Compared with M group,the volume ratio of cerebral infarction in B group mice was significantly reduced(P＜0.05).Compared with S group mice,M group mice showed a small amount of nuclear pyknosis and fission in the neurons of the CA1 and CA3 re-gions of the hippocampus.Compared with M group mice,group B mice showed enhanced nuclear pyknosis,nuclear fis-sion vacuoles,and necrosis in the CA1 and CA3 regions,but the B+M group antagonized this effect.Compared with S group,LC3 Ⅱ/Ⅰ,p-AMPK/AMPK of ischaemic brain tissue in M group rats increased(P＜0.05);compared with M group,B Group showed a decrease in LC3 Ⅱ/Ⅰ,p-AMPK/AMPK(P＜0.05).Compared with S group,the p-mTOR/mTOR and Ps757-ULK1/ULK1 ratio decreased in M group;compared with M group,the p-mTOR/mTOR and Ps757-ULK1/ULK1 ratio were significantly increased in B group(P＜0.05).Conclusion BAF-A1 pretreatment may exert a protective effect on neural function by inhibiting the AMPK/mTOR/ULK1 signaling pathway,thereby inhibiting excessive autophagy in the hippocampus of mice.
Bafilomycin A1/Cerebral ischemia-reperfusion injury/Adenosine activated protein kinase/Mammalian tar-get of rapamycin/UNC-51 like kinase 1/Neuroprotection
维普
万方数据