Effects of Different Reperfusion Sequence on Hepatic Ischemia-Reperfusion Injury_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GU Guowen , LI Xiangcheng , SUN Yong.

Living Donor Liver Transplantation Center, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaCorresponding Author: LI Xiang-cheng, E-mail: doclixc@hotmail.com;

Corresponding author：

Keywords：

Reperfusion injury; Hepatic artery; Portal vein; Oxygen radical

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　Objective 　To investigate the effects of different reperfusion sequence on hepatic warm ischemia-reperfusion injury and its related mechanisms.
　Methods 　Ninety-six healthy male Sprague Dawley rats were randomly divided into 6 groups by using random digits method (n=16, each)： Sham operation group, only shammed operation for negative control; the other 5 groups were all experimental groups, which were divided according to different reperfusion sequences of portal vein and hepatic artery: reperfusion first through the portal vein for 1 min with subsequent full reperfusion group, reperfusion first through the portal vein for 2 min with subsequent full reperfusion group, reperfusion first through the hepatic artery for 1 min with subsequent full reperfusion group, reperfusion first through the hepatic artery for 2 min with subsequent full reperfusion group, simultaneous reperfusion through the portal vein and hepatic artery group. Each group was further randomly divided into two subgroups (n=8, each) for sample collection at 2, 4 hours after reperfusion respectively. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA), superoxide dismutase (SOD) and glutathion (GSH) in hepatic tissue were detected respectively. HE staining of histopathologic slides was used to observe the morphological changes of hepatic tissue. TUNEL method was used to assess the apoptosis index (AI) of hepatocytes.
　Results 　The liver of rat was approximately normal in the sham operation group with lower levels of ALT, AST, MDA and AI, and higher levels of SOD and GSH as compared with all the experimental groups (P＜0.01). Less
hepatic ischemia-reperfusion injury was found in reperfusion first through the portal vein for 1 min with subsequent full reperfusion group, whose ALT, AST, MDA and AI levels were significantly lower than those of the other experimental groups (P＜0.05 or P＜0.01), and its SOD and GSH levels were higher than those of the other experimental groups (P＜0.05 or P＜0.01). HE staining also showed milder hepatic injury in reperfusion first through the portal vein for 1 min with subsequent full reperfusion group as compared with the other experimental groups.
　Conclusion　 Hepatic reperfusion first through portal vein for short time with subsequent full reperfusion could depress the synthesis of free oxygen radicals and suppress apoptosis of hepatocytes, thus relieving hepatic ischemia-reperfusion injury.

Citation： GU Guowen,LI Xiangcheng,SUN Yong.. Effects of Different Reperfusion Sequence on Hepatic Ischemia-Reperfusion Injury. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(3): 203-207. doi: Copy

1.	Romanque UP, Uribe MM, Videla LA. Molecular mechanisms in liver ischemic-reperfusion injury and ischemic preconditioning [Ｊ].　Rev Med Chil, 2005; 133(4):469.
2.	胡军, 刘志苏, 孙权, 等. 缺血后处理对肝脏缺血再灌注中肝窦内皮细胞损伤的保护作用 [Ｊ]. 肝脏， 2004; 9(1):21.
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6.	van As AB, Lotz Z, Tyler M, et al. Reperfusion injury associated with portal venous and hepatic arterial perfusion in liver transplantation [Ｊ].Transplantation, 2002; 74(2):158.
7.	Moreno C, Sabaté A, Figueras J, et al. Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft [Ｊ]. Liver Transpl, 2006; 12(11):1607.
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13.	Wu BQ, Chu WW, Zhang LY, et al. Protection of preconditioning, postconditioning and combined therapy against hepatic ischemia/reperfusion injury [Ｊ]. Chin J Traumatol, 2007; 10(4):223.
14.	冉江华, 郭永章, 李立, 等. 重组人生长激素对大鼠肝脏缺血再灌注损伤的保护作用 [Ｊ]. 中国普外基础与临床杂志， 2006; 13(5):555.
15.	王科, 王学浩, 张峰，等. 诱导HO-1改善氧化应激状态减轻老年供肝缺血-再灌注损伤 [Ｊ]. 中国普外基础与临床杂志, 2005; 12(2):109.
16.	Demirbilek S, Karaman A, Gürünlüoglu K, et al. Polyenylphosphatidylcholine pretreatment protects rat liver from ischemia/reperfusion injury [Ｊ]. Hepatol Res, 2006; 34(2):84.
17.	Yuan GJ, Ma JC, Gong ZJ, et al. Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats [Ｊ]. World J Gastroenterol, 2005; 11(12):1825.
18.	Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion [Ｊ]. Pharmacol Ther, 2007; 116(2):173.
19.	Davidson SM, Hausenloy D, Duchen MR, et al. Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection [Ｊ]. Int J Biochem Cell Biol, 2006; 38(3):414.
20.	Piper HM, Abdallah Y, Schfer C. The first minutes of reperfusion: a window of opportunity for cardioprotection [Ｊ]. Cardiovasc Res, 2004; 61(3):365.
21.	Kloner RA, Rezkalla SH. Preconditioning, postconditioning and their application to clinical cardiology [Ｊ]. Cardiovasc Res, 2006; 70(2):297.
22.	Yellon DM, Hausenloy DJ. Realizing the clinical potential of ischemic preconditioning and postconditioning [Ｊ]. Nat Clin Pract Cardiovasc Med, 2005; 2(11):568.
23.	Rastaldo R, Penna C, Cappello S, et al.Ischemic postconditioning: an effective strategy of myocardial protection? [Ｊ]. G Ital Cardiol (Rome), 2006; 7(7):464.

1. Romanque UP, Uribe MM, Videla LA. Molecular mechanisms in liver ischemic-reperfusion injury and ischemic preconditioning [Ｊ].　Rev Med Chil, 2005; 133(4):469.
2. 胡军, 刘志苏, 孙权, 等. 缺血后处理对肝脏缺血再灌注中肝窦内皮细胞损伤的保护作用 [Ｊ]. 肝脏， 2004; 9(1):21.
3. Galaris D, Barbouti A, Korantzopoulos P. Oxidative stress in hepatic ischemia-reperfusion injury: the role of antioxidants and iron chelating compounds [Ｊ]. Curr Pharm Des, 2006; 12(23):2875.
4. Sun K, Liu ZS, Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning [Ｊ]. World J Gastroenterol, 2004; 10(13):1934.
5. Puhl G, Schaser KD, Pust D, et al. The delay of rearterialization after initial portal reperfusion in living donor liver transplantation significantly determines the development of microvascular graft dysfunction [Ｊ]. J Hepatol, 2004; 41(2):299.
6. van As AB, Lotz Z, Tyler M, et al. Reperfusion injury associated with portal venous and hepatic arterial perfusion in liver transplantation [Ｊ].Transplantation, 2002; 74(2):158.
7. Moreno C, Sabaté A, Figueras J, et al. Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft [Ｊ]. Liver Transpl, 2006; 12(11):1607.
8. Polak WG, Porte RJ. The sequence of revascularization in liver transplantation: it does make a difference [Ｊ]. Liver Transpl, 2006; 12(11):1566.
9. Vinten-Johansen J, Zhao ZQ, Zatta AJ, et al. Postconditioning—A new link in nature’s armor against myocardial ischemia-reperfusion injury [Ｊ]. Basic Res Cardiol, 2005; 100(4):295.
10. Glantzounis GK, Salacinski HJ, Yang W, et al. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review [Ｊ]. Liver Transpl, 2005; 11(9):1031.
11. Zhang W, Wang M, Xie HY, et al. Role of reactive oxygen species in mediating hepatic ischemia-reperfusion injury and its therapeutic applications in liver transplantation [Ｊ]. Transplant Proc, 2007; 39(5):1332.
12. Becker LB. New concepts in reactive oxygen species and cardiovascular reperfusion physiology [Ｊ]. Cardiovasc Res, 2004; 61(3):461.
13. Wu BQ, Chu WW, Zhang LY, et al. Protection of preconditioning, postconditioning and combined therapy against hepatic ischemia/reperfusion injury [Ｊ]. Chin J Traumatol, 2007; 10(4):223.
14. 冉江华, 郭永章, 李立, 等. 重组人生长激素对大鼠肝脏缺血再灌注损伤的保护作用 [Ｊ]. 中国普外基础与临床杂志， 2006; 13(5):555.
15. 王科, 王学浩, 张峰，等. 诱导HO-1改善氧化应激状态减轻老年供肝缺血-再灌注损伤 [Ｊ]. 中国普外基础与临床杂志, 2005; 12(2):109.
16. Demirbilek S, Karaman A, Gürünlüoglu K, et al. Polyenylphosphatidylcholine pretreatment protects rat liver from ischemia/reperfusion injury [Ｊ]. Hepatol Res, 2006; 34(2):84.
17. Yuan GJ, Ma JC, Gong ZJ, et al. Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats [Ｊ]. World J Gastroenterol, 2005; 11(12):1825.
18. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion [Ｊ]. Pharmacol Ther, 2007; 116(2):173.
19. Davidson SM, Hausenloy D, Duchen MR, et al. Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection [Ｊ]. Int J Biochem Cell Biol, 2006; 38(3):414.
20. Piper HM, Abdallah Y, Schfer C. The first minutes of reperfusion: a window of opportunity for cardioprotection [Ｊ]. Cardiovasc Res, 2004; 61(3):365.
21. Kloner RA, Rezkalla SH. Preconditioning, postconditioning and their application to clinical cardiology [Ｊ]. Cardiovasc Res, 2006; 70(2):297.
22. Yellon DM, Hausenloy DJ. Realizing the clinical potential of ischemic preconditioning and postconditioning [Ｊ]. Nat Clin Pract Cardiovasc Med, 2005; 2(11):568.
23. Rastaldo R, Penna C, Cappello S, et al.Ischemic postconditioning: an effective strategy of myocardial protection? [Ｊ]. G Ital Cardiol (Rome), 2006; 7(7):464.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Different Reperfusion Sequence on Hepatic Ischemia-Reperfusion Injury

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