Volume 22 Issue 2
Feb.  2024
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ZHOU Chaorui, GU Jiankun, CHEN Na, LI Mingjuan. Neuroprotective effect of Bafilomycin A1 on cerebral ischaemia reperfusion injury by regulation AMPK/mTOR/ULK1 signaling pathway in mice[J]. Chinese Journal of General Practice, 2024, 22(2): 225-229. doi: 10.16766/j.cnki.issn.1674-4152.003371
Citation: ZHOU Chaorui, GU Jiankun, CHEN Na, LI Mingjuan. Neuroprotective effect of Bafilomycin A1 on cerebral ischaemia reperfusion injury by regulation AMPK/mTOR/ULK1 signaling pathway in mice[J]. Chinese Journal of General Practice, 2024, 22(2): 225-229. doi: 10.16766/j.cnki.issn.1674-4152.003371

Neuroprotective effect of Bafilomycin A1 on cerebral ischaemia reperfusion injury by regulation AMPK/mTOR/ULK1 signaling pathway in mice

doi: 10.16766/j.cnki.issn.1674-4152.003371
Funds:

 LGD21H300001

  • Received Date: 2023-11-14
    Available Online: 2024-03-27
  •   Objective  To investigate the mechanism by which bafilomycin A1 (BAF-A1) attenuates cerebral ischemia-reperfusion (IR) injury in mice by regulating autophagy through the adenosine activated protein kinase (AMPK)/mammalian 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 significant 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 regions of the hippocampus. Compared with M group mice, group B mice showed enhanced nuclear pyknosis, nuclear fission 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.

     

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