Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage  

作　　者：Xuecheng Zheng Junling Gao Manman Zhao Lingling Han Dexin Zhang Kaijie Wang Jianzhong Cui 

机构地区：[1]Department of Surgery,Hebei Medical University,Shijiazhuang,Hebei 050017,China [2]Department of Histology and Embryology,North China University of Science and Technology,Tangshan,Hebei 063000,China [3]Department of Neurosurgery,Tangshan Gongren Hospital,Tangshan,Hebei 063000,China

出　　处：《Chinese Medical Journal》2023年第6期719-731,共13页中华医学杂志（英文版）

基　　金：Natural Science Foundation of Hebei Province(No.H2019105137)

摘　　要：Background:Sirtuin-3(Sirt3)has been documented to protect against mitochondrial dysfunction and apoptosis.Honokiol(HKL)is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders.The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage(ICH).Methods:An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia.PC12 cells were stimulated with hemin.For the in vivo investigation,the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits.Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis.Immunohistochemical staining was used to investigate the expression of Sirt3.Adenosine triphosphate(ATP)levels were quantified to assess mitochondrial dysfunction.Cell counting kit-8,lactate dehydrogenase assay,and flow cytometry were used to analyze cell vitality and apoptosis in vitro.Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1(Drp1)localization to mitochondria.Western blot was applied to quantify the expression of Sirt3,Bax,Bcl-2,cleaved-caspase-3,Drp1,phosphorylation of Drp1 at serine-616,and phosphorylation of Drp1 at serine-637 in vivo and in vitro.Results:HKL treatment alleviated neurological deficits,attenuated the histopathological damage and cell apoptosis,and restored the decreased ATP levels in ICH rats.HKL improved cell survival rate,reduced cell apoptosis,and inhibited mitochondrial fission in PC12 cells.Moreover,both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616,and reduced phosphorylation of Drp1 at Ser637.Meanwhile,immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells.The phosphorylation and mitochondrial translocation of Drp1

关 键 词：APOPTOSIS Drp1 HONOKIOL Intracerebral hemorrhage Mitochondrial fission Sirt3 

分 类 号：R743.34[医药卫生—神经病学与精神病学]