title: Human heat shock protein 27 exacerbates ischemia reperfusion injury in rats by reducing the number of T regulatory cells.
abstract: Ischemia reperfusion injury (IRI) occurs in almost every liver surgery and is associated with the reduction of the liver blood flow. Ischemia impairs liver function and can even cause liver failure following surgery. The present study aimed to identify a new molecular target allowing the reduction of IRI and explore the related cellular mechanism. Adenovirus (~2.5x10(12) viral particles) bearing the human heat shock protein 27 (HSP27) gene was injected into rat liver through the ileocecal vein. Five days following the injection, ischemia was induced by clamping the median and left portal veins, hepatic arteries and bile ducts. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and superoxide dismutase (SOD) were measured. The infiltration of inflammatory cells and the expression of pro-inflammatory factors were investigated. The number of regulatory T cells (Tregs) was measured by flow cytometry. At 2 h following reperfusion, the group injected with HSP27 had the highest level of ALT and AST, followed by the group injected with HSP27 and treated with gadolinium trichloride (GdCl3), the empty vector-injected and the vector+GdCl3 groups. The HSP27 group also had the lowest levels of the oxidative stress-protective factors SOD and GSH, and the highest levels of pro-inflammatory factors. The number of Tregs was reduced in the groups injected with HSP27. In conclusion, the human HSP27 protein can effectively accelerate liver damage at the early stages of IRI in rats. Tregs might play a critical role in HSP27‑induced liver injury.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Sunyi
authors.initials: S
authors.lastname: Ye
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Combined Multi‑Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Key Laboratory of Combined Multi‑Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Combined Multi‑Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008954:Models, Biological; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D055551:HSP27 Heat-Shock Proteins