title: Propofol postconditioning attenuates hippocampus ischemia-reperfusion injury via modulating JAK2/STAT3 pathway in rats after autogenous orthotropic liver transplantation.
abstract: Liver transplantation has been a routine treatment for the end stage liver diseases. Severe changes in circulation system and internal environment may occur during transplant surgery and cause injury to many organs including brain. Specific mechanisms of brain injury associated with liver transplantation are not yet elucidated. Previous studies have shown that the JAK/STAT signal transduction pathways are involved in the development of the central nervous system, such as nerve cell proliferation, survival, differentiation, and it also have a role in the disease processes, including brain tumor, brain ischemia and other diseases of the central nervous system. In this study we investigate whether propofol plays an important role in protecting the hippocampus through JAK2/STAT3 pathway. Thirty-two healthy male Sprague-Dawley rats, were randomly divided into four groups (n=8). Sham operation group (group S), autogenous orthotropic liver transplantation group (group I), autogenous orthotropic liver transplantation+propofol treatment group (group P) and autogenous orthotropic liver transplantation+propofol+AG490 treatment group (group A). We evaluated histological damage, inflammation, oxidative stress and apoptosis in hippocampus using HE staining, light microscope, real-time PCR and western blot. The results showed that there was a significant damage of hippocampus in group I compared to the sham group as demonstrated by increased serum levels of S100β, NSE and the histological changes. However, an induction of propofol reduced the levels of MDA, TNFα, S100β, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3, meanwhile. Consistently, pretreatment with JAK2/STAT3 pathway inhibitor AG490, decreased the levels of MDA, TNFα, S100β, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3. These results reveal that autogenous orthotropic liver transplantation induces the activation of JAK2/STAT3 signaling pathway in hippocampus. Pretreatment with propofol attenuates autogenous orthotropic liver transplantation induces hippocampal injury via JAK2/STAT3 pathway.
authors.affiliation: First Center Hospital, 24 Fukang road, Tianjin 300192, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Jia
authors.affiliation: The First Center Clinic College, Tianjin Medical University, 22 Qixiangtai road, Tianjin 300070, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Plastic surgery, Taizhou People's Hospital Affiliated to Nantong and Jiangsu University, Taizhou, Jiangsu 225300, PR China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Gu
authors.affiliation: First Center Hospital, 24 Fukang road, Tianjin 300192, PR China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Weng
authors.affiliation: First Center Hospital, 24 Fukang road, Tianjin 300192, PR China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Sheng
authors.affiliation: First Center Hospital, 24 Fukang road, Tianjin 300192, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The People's Hospital of Jiaozuo City, Jiaozuo, Henan 454002, PR China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Li
authors.affiliation: First Center Hospital, 24 Fukang road, Tianjin 300192, PR China.
authors.forename: Hongyin
authors.initials: H
authors.lastname: Du
authors.affiliation: First Center Hospital, 24 Fukang road, Tianjin 300192, PR China. Electronic address: yzxyuwenli@163.com.
authors.forename: Wenli
authors.initials: W
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D053614:Janus Kinase 2 / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014182:Transplantation, Autologous / Q000009:adverse effects
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D015742:Propofol
keywords: Hippocampus; JAK/STAT; Liver transplantation; Propofol