title: Berberine protects against ischemia/reperfusion injury after orthotopic liver transplantation via activating Sirt1/FoxO3α induced autophagy.
abstract: The effects and mechanism of berberine (BBR) on hepatic injury after orthotopic liver transplantation (OLT) have not been well characterized. We examined the role of Sirt1/FoxO3α axis in the protective effect of BBR on ischemia/reperfusion injury after OLT. Adult male Wistar rats were randomly allocated into four groups: Sham, OLT, OLT with BBR pretreatment (BBR), OLT with BBR and Sirt1 inhibitor (EX527) pretreatment group (EX527). The liver function and oxidative stress level were measured by biochemical and histopathologic examinations. The formation of autophagosome was observed by transmission electron microscopy. The apoptotic rate was determined by TUNEL analysis and the apoptotic mRNA expression. The expression of Sirt1, FoxO3α, Beclin-1, LC3-II/LC3-I, p62 and the acetylation of FoxO3α were assayed by western blot assay and immunoprecipitation. Compared with the OLT group, BBR dramatically attenuated the histopathologic damage, restored the liver function, and decreased the oxidative stress level. Simultaneously, BBR significantly ameliorated apoptosis by decreasing the apoptotic rate and the expression of apoptotic mRNA in rats subjected to OLT. The level of Beclin-1 and LC3-II/LC3-I were upregulated with the inhibition of p62. The deacetylation of FoxO3α by Sirt1 was enhanced in the nuclear of liver after pretreated with BBR. However, the inhibition of Sirt1 by EX527 counteracted the protective effects of BBR. Thus, BBR preconditioning promotes liver transplant ischemia/reperfusion injury partly via activating Sirt1/FoxO3α mediated autophagy.
authors.affiliation: The Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China.
authors.forename: Yuanbang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: The Department of Anesthesiology, Tianjin First Center Hospital, 24 Fukang Road, Tianjin 300192, PR China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Sheng
authors.affiliation: The Department of Anesthesiology, Tianjin First Center Hospital, 24 Fukang Road, Tianjin 300192, PR China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Weng
authors.affiliation: The Department of Anesthesiology, Tianjin First Center Hospital, 24 Fukang Road, Tianjin 300192, PR China.
authors.forename: Rubin
authors.initials: R
authors.lastname: Xu
authors.affiliation: The Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: The Department of Anesthesiology, Tianjin First Center Hospital, 24 Fukang Road, Tianjin 300192, PR China.
authors.forename: Hongyin
authors.initials: H
authors.lastname: Du
authors.affiliation: The Department of Anesthesiology, Tianjin First Center Hospital, 24 Fukang Road, Tianjin 300192, PR China. Electronic address: yuwenli999@sina.com.
authors.forename: Wenli
authors.initials: W
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D020011:Protective Agents; D001599:Berberine; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Apoptosis; Autophagy; Berberine; Liver transplantation; Sirtuin 1