title: Ulinastatin preconditioning attenuates inflammatory reaction of hepatic ischemia reperfusion injury in rats via high mobility group box 1(HMGB1) inhibition.
abstract: Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear. This study aims to investigate possible pathomechanism of ulinastatin in reducing the inflammatory response after hepatic IR. Methods A male sprague-dawley(SD) rat model of hepatic ischemia reperfusion injury was used. The rats were randomly divided into 4 groups on average, which were 0.9% saline and IR group as control, ulinastatin preconditioning (UPC) group, UPC+rHMGB1 (recombinant HMGB1) group and UPC +anti-HMGB1 group. Serum aminotransferases, TNF-α, IL-1 and Myeloperoxidase (MPO) levels were measured. Histopathology examination and apoptotic cell detection and the different expression of HMGB1 protein were also assessed. Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05). Decreased histologic damage and apoptosis were also seen in these two groups (p<0.05). Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.
authors.affiliation: 1. Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tong
authors.affiliation: 2. Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: 3. Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: 4. Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 4. Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Yang
authors.affiliation: 5. Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Shen
authors.affiliation: 5. Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D006023:Glycoproteins; D024243:HMGB1 Protein; D014361:Trypsin Inhibitors; D009195:Peroxidase; D000637:Transaminases; D001219:Aspartate Aminotransferases; C028665:urinastatin
keywords: High mobility group box 1 protein (HMGB1); Ischemia reperfusion; Preconditioning; Ulinastatin