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缺血后处理对大鼠肝脏热/冷缺血再灌注损伤的保护作用:与缺血预处理的比较研究

Protective effects of ischaemic postconditioning on warm/cold ischaemic reperfusion injury in rat liver: a comparative study with ischaemic preconditioning.

作者信息

Wang Ke-xin, Hu San-yuan, Jiang Xu-sheng, Zhu Min, Jin Bin, Zhang Guang-yong, Chen Bo

机构信息

Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.

出版信息

Chin Med J (Engl). 2008 Oct 20;121(20):2004-9.

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 gamma 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.

摘要

背景

在肝脏大手术期间,缺血再灌注损伤(IRI)不可避免。缺血预处理(IPC)已被证明是一种针对肝脏IRI的有效干预措施。最近,有研究表明缺血后处理(IPO)对IRI具有有效的心脏保护作用。我们通过与IPC比较,评估了IPO对大鼠肝脏热/冷IRI的保护作用,并评估了细胞凋亡在此过程中的作用。

方法

建立热IRI模型(肝蒂夹闭30分钟)和冷IRI模型(原位肝移植并冷保存2小时)。每个模型分为3组:(1)对照组,正常热/冷IRI;(2)IPC组,在热/冷IRI之前进行2次5分钟缺血后再灌注5分钟;(3)IPO组,在热/冷缺血后进行3次30秒再灌注后再闭塞30秒。比较术后3小时血清转氨酶、葡萄糖以及胆汁中γ-谷氨酰转移酶(GGT)水平、组织病理学检查、肝细胞凋亡活性和凋亡相关蛋白Fas。还比较了干预1周后的生存率。

结果

与对照组相比,IPO和IPC均保护了肝细胞和胆管上皮细胞的功能,通过阻止Fas基因表达抑制了肝细胞凋亡,并提高了两个模型1周生存率(P<0.05)。IPO组和IPC组在血清转氨酶水平、葡萄糖、胆汁中GGT水平、Fas阳性表达指数和1周生存率方面相当。在冷缺血模型中,IPO的凋亡指数低于IPC(P<0.05)。

结论

与缺血预处理相比,缺血后处理对大鼠肝脏热或冷缺血再灌注损伤具有相当的保护作用。

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