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Protective effects of ischaemic postconditioning on warm/cold ischaemic reperfusion injury in rat liver: a comparative study with ischaemic preconditioning
作者单位:Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China 
基金项目:Acknowledgements: We are sincerely grateful to Prof. LIU Yan-xun for the help of statistical analysis, and to Prof. Eldo Frezza and Prof. XI Yao-sheng for the help of early literal revision.
摘    要:Background Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated that ischaemic postconditioning (IPO) provided effective cardioprotection on IRI. We evaluated the protective effects of IPO on warm/cold IRI in rat liver by a comparison with IPC and assessed the role of apoptosis in the process.
Methods Warm IRI model (clamping hepatic pedicle for 30 minutes) and cold IRI model (orthotopic liver transplantation with 2 hours cold storage) were established. Each model consisted of 3 groups: (1) control group, normal warm/cold IRI; (2) IPC group, 5 minutes of ischaemia followed by 5 minutes of reperfusion twice prior to warm/cold IRI; (3) IPO group, 30 seconds of reperfusion followed by 30 seconds of reocclusion for three times after warm/cold ischaemia. The levels of serum transaminase, glucose, and γ glutamyltransferase (GGT) in bile, histopathological examination, apoptotic activity of hepatocyte, and apoptosis related protein Fas, at 3 hours after operation were compared. Survival rates one week after intervention were also compared.
Results IPO and IPC protected the functions of hepatocytes and biliary epithelial cells, inhibited the hepatocellular apoptosis by preventing expression of Fas gene, and elevated the one week survival rate compared with control group in both models (P 〈0.05). IPO and IPC groups were comparable in levels of serum transaminase levels, glucose, and GGT in bile, Fas positive expression index, and one week survival. In cold ischaemic models, IPO had lower apoptotic index than IPC (P 〈0.05).
Conclusion Compared with ischaemic preconditioning, ischaemic postconditioning is associated with comparable protections of rat liver from warm or cold ischaemic reperfusion injury.

关 键 词:肝疾病  预处理  缺血损伤  治疗方法  临床表现

Protective effects of ischaemic postconditioning on warm/cold ischaemic reperfusion injury in rat liver: a comparative study with ischaemic preconditioning
Authors:WANG Ke-xin  HU San-yuan  JIANG Xu-sheng  ZHU Min  JIN Bin  ZHANG Guang-yong  CHEN Bo
Institution:WANG Ke-xin(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);HU San-yuan(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);JIANG Xu-sheng(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);ZHU Min(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);JIN Bin(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);ZHANG Guang-yong(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);CHEN Bo(Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China);
Abstract:Background Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated that ischaemic postconditioning (IPO) provided effective cardioprotection on IRI. We evaluated the protective effects of IPO on warm/cold IRI in rat liver by a comparison with IPC and assessed the role of apoptosis in the process. Methods Warm IRI model (clamping hepatic pedicle for 30 minutes) and cold IRI model (orthotopic liver transplantation with 2 hours cold storage) were established. Each model consisted of 3 groups: (1) control group, normal warm/cold IRI; (2) IPC group, 5 minutes of ischaemia followed by 5 minutes of reperfusion twice prior to warm/cold IRI; (3) IPO group, 30 seconds of reperfusion followed by 30 seconds of reocclusion for three times after warm/cold ischaemia. The levels of serum transaminase, glucose, and y glutamyltransferase (GOT) in bile, histopathological examination, apoptotic activity of hepatocyte, and apoptosis related protein Fas, at 3 hours after operation were compared. Survival rates one week after intervention were also compared.Results IPO and IPC protected the functions of hepatocytes and biliary epithelial cells, inhibited the hepatocellular apoptosis by preventing expression of Fas gene, and elevated the one week survival rate compared with control group in both models (P<0.05). IPO and IPC groups were comparable in levels of serum transaminase levels, glucose, and GGT in bile, Fas positive expression index, and one week survival. In cold ischaemic models, IPO had lower apoptotic index than IPC (P<0.05).Conclusion Compared with ischaemic preconditioning, ischaemic postconditioning is associated with comparable protections of rat liver from warm or cold ischaemic reperfusion injury.
Keywords:liver  ischaemic preconditioning  ischaemic postconditioning  reperfusion injury  apoptosis
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