• 南京醫(yī)科大學(xué)第一附屬醫(yī)院肝臟外科，活體肝移植中心(南京210029);

目的 　研究大鼠肝臟熱缺血后經(jīng)門靜脈和肝動(dòng)脈不同時(shí)序灌注對(duì)其損傷的影響，探索是否可由此減輕大鼠肝臟缺血再灌注損傷及其可能的機(jī)理。
方法 　選用健康雄性SD大鼠96只，按隨機(jī)數(shù)字表法等分成6組，1組為假手術(shù)組，其余5組為實(shí)驗(yàn)組。假手術(shù)組(16只)只作開腹和肝門部解剖; 實(shí)驗(yàn)組(共5組，每組16只)根據(jù)再灌注時(shí)門靜脈和肝動(dòng)脈不同開放時(shí)序分組： 先開放門靜脈1 min后再開放肝動(dòng)脈組、先開放門靜脈2 min后再開放肝動(dòng)脈組、先開放肝動(dòng)脈1 min后再開放門靜脈組、先開放肝動(dòng)脈2 min后再開放門靜脈組及同時(shí)開放門靜脈和肝動(dòng)脈組。各組分別于術(shù)后2 h和4 h檢測(cè)血清中ALT和AST值，肝組織中丙二醛（MDA）、超氧化物歧化酶（SOD）及谷胱甘肽（GSH）含量變化； 采用病理組織切片HE染色觀察肝組織損傷情況；　TUNEL法檢測(cè)各組肝組織細(xì)胞凋亡情況。
結(jié)果 　假手術(shù)組大鼠肝臟基本正常，各指標(biāo)均好于各實(shí)驗(yàn)組，差異均有統(tǒng)計(jì)學(xué)意義(P＜0.01)。在各實(shí)驗(yàn)組中先開放門靜脈1 min后再開放肝動(dòng)脈組大鼠肝臟缺血再灌注損傷最輕，其ALT、AST、MDA和凋亡指數(shù)值均明顯低于其他各實(shí)驗(yàn)組，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05或P＜0.01)，并且其SOD和GSH值均高于其他各實(shí)驗(yàn)組，差異亦有統(tǒng)計(jì)學(xué)意義(P＜0.05或P＜0.01)。肝組織HE染色也顯示，先開放門靜脈1 min后再開放肝動(dòng)脈組大鼠肝組織損傷較其他各實(shí)驗(yàn)組輕。
結(jié)論 　肝臟熱缺血后，通過短暫開放門靜脈再開放肝動(dòng)脈的措施可以減輕大鼠肝臟缺血再灌注損傷，可能與降低活性氧的產(chǎn)生及保護(hù)肝臟抗氧化系統(tǒng)有關(guān)。

引用本文： 顧國文,李相成,孫勇. 肝門阻斷時(shí)肝動(dòng)脈與門靜脈不同開放時(shí)序?qū)Ω闻K缺血再灌注的影響. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(3): 203-207. doi: 復(fù)制

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. 胡軍, 劉志蘇, 孫權(quán), 等. 缺血后處理對(duì)肝臟缺血再灌注中肝竇內(nèi)皮細(xì)胞損傷的保護(hù)作用 [Ｊ]. 肝臟， 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. 冉江華, 郭永章, 李立, 等. 重組人生長激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2006; 13(5):555.
15. 王科, 王學(xué)浩, 張峰， 等. 誘導(dǎo)HO-1改善氧化應(yīng)激狀態(tài)減輕老年供肝缺血-再灌注損傷 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 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. 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. 2. 胡軍, 劉志蘇, 孫權(quán), 等. 缺血后處理對(duì)肝臟缺血再灌注中肝竇內(nèi)皮細(xì)胞損傷的保護(hù)作用 [Ｊ]. 肝臟， 2004; 9(1):21.
  3. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. Becker LB. New concepts in reactive oxygen species and cardiovascular reperfusion physiology [Ｊ]. Cardiovasc Res, 2004; 61(3):461.
  13. 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. 14. 冉江華, 郭永章, 李立, 等. 重組人生長激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志， 2006; 13(5):555.
  15. 15. 王科, 王學(xué)浩, 張峰， 等. 誘導(dǎo)HO-1改善氧化應(yīng)激狀態(tài)減輕老年供肝缺血-再灌注損傷 [Ｊ]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12(2):109.
  16. 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. 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. 18. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion [Ｊ]. Pharmacol Ther, 2007; 116(2):173.
  19. 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. 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. 21. Kloner RA, Rezkalla SH. Preconditioning, postconditioning and their application to clinical cardiology [Ｊ]. Cardiovasc Res, 2006; 70(2):297.
  22. 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. 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.