Puerarin protects rat brain against ischemia/reperfusion injury by suppressing autophagy via the AMPK-mTOR-ULK1 signaling pathway
Jin-Feng Wang
Zhi-Gang Mei
Yang Fu
Song-Bai Yang
Shi-Zhong Zhang
Wei-Feng Huang
Li Xiong
Hua-Jun Zhou
Wei Tao
Zhi-Tao Feng
摘要：Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury,and accumulating evidence indicates that the AMPK-mTOR signaling pathway regulates the activation of the autophagy pathway through the coordinated phosphorylation of ULK1.In this study,we investigated the mechanisms underlying the neuroprotective effect of puerarin and its role in modulating autophagy via the AMPK-mTOR-ULK1 signaling pathway in the rat middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury.Rats were intraperitoneally injected with puerarin,50 or 100 mg/kg,daily for 7 days.Then,30 minutes after the final administration,rats were subjected to transient middle cerebral artery occlusion for 90 minutes.Then,after 24 hours of reperfusion,the Longa score and infarct volume were evaluated in each group.Autophagosome formation was observed by transmission electron microscopy.LC3,Beclin-1 p62,AMPK,mTOR and ULK1 protein expression levels were examined by immunofluorescence and western blot assay.Puerarin substantially reduced the Longa score and infarct volume,and it lessened autophagosome formation in the hippocampal CA1 area following cerebral ischemia/reperfusion injury in a dose-dependent manner.Pretreatment with puerarin (50 or 100 mg/kg) reduced Beclin-1 expression and the LC3-Ⅱ/LC3-Ⅰ ratio,as well as p-AMPK and pS317-ULK1 levels.In comparison,it increased p62 expression.Furthermore,puerarin at 100 mg/kg dramatically increased the levels of p-mTOR and pS757-ULK1 in the hippocampus on the ischemic side.Our findings suggest that puerarin alleviates autophagy by activating the APMK-mTOR-ULK1 signaling pathway.Thus,puerarin might have therapeutic potential for treating cerebral ischemia/reperfusion injury.
机标关键词：
资助基金：the National Natural Science Foundation of China,(No.81202625)the Open Fund of Key Laboratory of Cardiovascular and Cerebrovascular Diseases Translational Medicine,China Three Gorges University,China,(No.2016xnxg101)
论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 989-998 )
英文信息