• 安徽醫(yī)科大學(xué)第一附屬醫(yī)院肝膽外科(合肥230022);

目的:總結(jié)肝臟缺血預(yù)處理（ischemic preconditioning，IPC）的保護機理及其在肝切除、肝移植中的臨床研究進展。方法:復(fù)習(xí)近年來肝臟IPC的基礎(chǔ)和臨床研究的文獻。 ]
結(jié)果:實驗研究表明，IPC主要通過維持和改善肝臟能量代謝、改善微循環(huán)障礙、減輕脂質(zhì)過氧化和氧自由基的產(chǎn)生、抑制炎性細胞的激活和細胞因子的釋放、抑制細胞凋亡、誘導(dǎo)內(nèi)源性保護物質(zhì)的釋放等途徑保護肝臟缺血再灌注（ischemiareperfusion，IR）損傷； 目前多數(shù)臨床研究肯定了肝臟IPC的保護作用，但也有報道顯示IPC不能保護肝臟IR損傷。
結(jié)論:肝臟IPC能夠減輕肝臟IR損傷，但其在肝切除及其肝移植中的臨床應(yīng)用價值有待進一步的研究。

引用本文： 葉伯根,耿小平. 肝臟缺血預(yù)處理的研究進展. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(4): 303-306. doi: 復(fù)制

1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium [J]. Circulation, 1986; 74(5)∶1124.
2. Dehni N, Chazouilleres O, Vaubourdolle M, et al. Does the preconditioning effect work in normothermic liver ischemia? A study of the isolated perfused rat liver [J]. Hepatology, 1994; 20(2)∶394.
3. Riksen NP, Smits P, Rongen GA. Ischaemic preconditioning: from molecular characterisation to clinical application——part Ⅰ [J]. Neth J Med, 2004; 62(10)∶353.
4. Jaeschke H. Molecular mechanisms of hepatic ischemiareperfusion injury and preconditioning [J]. Am J Physiol Gastrointest Liver Physiol， 2003; 284(1)∶G15.
5. Kerem M, Bedirli A, Ofluoglu E, et al. Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats [J]. Liver Int， 2006; 26(8)∶994.
6. Clavien PA, Selzner M, Rüdiger HA, et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning [J]. Ann Surg， 2003; 238(6)∶843.
7. Sakamoto N, Sun Z, Brengman ML, et al. Hepatic reticuloendothelial system dysfunction after ischemiareperfusion: role of Pselectinmediated neutrophil accumulation [J]. Liver Transpl， 2003; 9(9)∶940.
8. Peralta C, Fernández L, Panés J, et al. Preconditioning protects against systemic disorders associated with hepatic ischemiareperfusion through blockade of tumor necrosis factorinduced Pselectin upregulation in the rat [J]. Hepatology， 2001; 33(1)∶100.
9. Caban A, Oczkowicz G, AbdelSamad O, et al. Influence of ischemic preconditioning and nitric oxide on microcirculation and the degree of rat liver injury in the model of ischemia and reperfusion [J]. Transplant Proc， 2006; 38(1)∶196.
10. Tejima K, Arai M, Ikeda H, et al. Ischemic preconditioning protects hepatocytes via reactive oxygen species derived from Kupffer cells in rats [J]. Gastroenterology， 2004; 127(5)∶1488.
11. Serafín A, RosellóCatafau J, Prats N, et al. Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusion [J]. Hepatology， 2004; 39(3)∶688.
12. Cheng XD, Jiang XC, Liu YB, et al. Effect of ischemic preconditioning on Pselectin expression in hepatocytes of rats with cirrhotic ischemiareperfusion injury [J]. World J Gastroenterol， 2003; 9(10)∶2289.
13. Quireze C, Montero EF, Leito RM, et al. Ischemic preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemiareperfusion injury in rats [J]. J Invest Surg， 2006; 19(4)∶229.
14. 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.
15. 馬躍峰 , 李相成, 姚愛華， 等. 缺血預(yù)處理對大鼠肝臟移植物再灌注早期NFκB活性的影響及意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5)∶531.
16. Mallick IH, Yang W, Winslet MC, et al. Protective effects of ischemic preconditioning on the intestinal mucosal microcirculation following ischemiareperfusion of the intestine [J]. Microcirculation， 2005; 12(8)∶615.
17. 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.
18. Xiao JS, Cai FG, Niu Y, et al. Preconditioning effects on expression of protooncogenes cfos and cjun after hepatic ischemia/reperfusion in rats [J]. Hepatobiliary Pancreat Dis Int， 2005; 4(2)∶197.
19. Cai FG, Xiao JS, Ye QF. Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats [J]. World J Gastroenterol， 2006; 12(18)∶2936.
20. Clavien PA, Yadav S, Sindram D, et al. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans [J]. Ann Surg， 2000; 232(2)∶155.
21. Nuzzo G, Giuliante F, Vellone M, et al. Pedicle clamping with ischemic preconditioning in liver resection [J]. Liver Transpl， 2004; 10(2 Suppl 1)∶S53.
22. 梁力建， 李紹強， 黃潔夫. 缺血預(yù)處理對肝硬化肝癌患者入肝血流阻斷肝切除的保護作用及其機理探討 [J]. 中華外科雜志, 2002; 40(4)∶265.
23. Li SQ, Liang LJ, Huang JF, et al. Ischemic preconditioning protects liver from hepatectomy under hepatic inflow occlusion for hepatocellular carcinoma patients with cirrhosis [J]. World J Gastroenterol， 2004; 10(17)∶2580.
24. Azoulay D, Lucidi V, Andreani P, et al. Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study [J]. J Am Coll Surg， 2006; 202(2)∶203.
25. 秦嵩, 孫備, 許軍, 等. 缺血預(yù)處理對大鼠肝臟低溫保存損傷的保護作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2003; 10(4)∶323.
26. Compagnon P, Lindell S, Ametani MS, et al. Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals [J]. Transplantation， 2005; 79(10)∶1393.
27. Niemann CU, Hirose R, Liu T, et al. Ischemic preconditioning improves energy state and transplantation survival in obese Zucker rat livers [J]. Anesth Analg， 2005; 101(6)∶1577.
28. Azoulay D, Del Gaudio M, Andreani P, et al. Effects of 10 minutes of ischemic preconditioning of the cadaveric liver on the graft’s preservation and function: the ying and the yang [J]. Ann Surg， 2005; 242(1)∶133.
29. Koneru B, Fisher A, He Y, et al. Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy [J]. Liver Transpl， 2005; 11(2)∶196.
30. Cescon M, Grazi GL, Grassi A, et al. Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study [J]. Liver Transpl， 2006; 12(4)∶628.
31. Kadono J, Hamada N, Fukueda M, et al. Advantage of ischemic preconditioning for hepatic resection in pigs [J]. J Surg Res， 2006; 134(2)∶173.
32. Rüdiger HA, Kang KJ, Sindram D, et al. Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver [J]. Ann Surg， 2002; 235(3)∶400.
33. Petrowsky H, McCormack L, Trujillo M, et al. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection [J]. Ann Surg， 2006; 244(6)∶921.
34. Smyrniotis V, Kostopanagiotou G, Theodoraki K, et al. Ischemic preconditioning versus intermittent vascular inflow control during major liver resection in pigs [J]. World J Surg， 2005; 29(7)∶930.
35. Eipel C, Glanemann M, Nuessler AK, et al. Ischemic preconditioning impairs liver regeneration in extended reducedsize livers [J]. Ann Surg， 2005; 241(3)∶477.
  1. 1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium [J]. Circulation, 1986; 74(5)∶1124.
  2. 2. Dehni N, Chazouilleres O, Vaubourdolle M, et al. Does the preconditioning effect work in normothermic liver ischemia? A study of the isolated perfused rat liver [J]. Hepatology, 1994; 20(2)∶394.
  3. 3. Riksen NP, Smits P, Rongen GA. Ischaemic preconditioning: from molecular characterisation to clinical application——part Ⅰ [J]. Neth J Med, 2004; 62(10)∶353.
  4. 4. Jaeschke H. Molecular mechanisms of hepatic ischemiareperfusion injury and preconditioning [J]. Am J Physiol Gastrointest Liver Physiol， 2003; 284(1)∶G15.
  5. 5. Kerem M, Bedirli A, Ofluoglu E, et al. Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats [J]. Liver Int， 2006; 26(8)∶994.
  6. 6. Clavien PA, Selzner M, Rüdiger HA, et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning [J]. Ann Surg， 2003; 238(6)∶843.
  7. 7. Sakamoto N, Sun Z, Brengman ML, et al. Hepatic reticuloendothelial system dysfunction after ischemiareperfusion: role of Pselectinmediated neutrophil accumulation [J]. Liver Transpl， 2003; 9(9)∶940.
  8. 8. Peralta C, Fernández L, Panés J, et al. Preconditioning protects against systemic disorders associated with hepatic ischemiareperfusion through blockade of tumor necrosis factorinduced Pselectin upregulation in the rat [J]. Hepatology， 2001; 33(1)∶100.
  9. 9. Caban A, Oczkowicz G, AbdelSamad O, et al. Influence of ischemic preconditioning and nitric oxide on microcirculation and the degree of rat liver injury in the model of ischemia and reperfusion [J]. Transplant Proc， 2006; 38(1)∶196.
  10. 10. Tejima K, Arai M, Ikeda H, et al. Ischemic preconditioning protects hepatocytes via reactive oxygen species derived from Kupffer cells in rats [J]. Gastroenterology， 2004; 127(5)∶1488.
  11. 11. Serafín A, RosellóCatafau J, Prats N, et al. Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusion [J]. Hepatology， 2004; 39(3)∶688.
  12. 12. Cheng XD, Jiang XC, Liu YB, et al. Effect of ischemic preconditioning on Pselectin expression in hepatocytes of rats with cirrhotic ischemiareperfusion injury [J]. World J Gastroenterol， 2003; 9(10)∶2289.
  13. 13. Quireze C, Montero EF, Leito RM, et al. Ischemic preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemiareperfusion injury in rats [J]. J Invest Surg， 2006; 19(4)∶229.
  14. 14. 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.
  15. 15. 馬躍峰 , 李相成, 姚愛華， 等. 缺血預(yù)處理對大鼠肝臟移植物再灌注早期NFκB活性的影響及意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5)∶531.
  16. 16. Mallick IH, Yang W, Winslet MC, et al. Protective effects of ischemic preconditioning on the intestinal mucosal microcirculation following ischemiareperfusion of the intestine [J]. Microcirculation， 2005; 12(8)∶615.
  17. 17. 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.
  18. 18. Xiao JS, Cai FG, Niu Y, et al. Preconditioning effects on expression of protooncogenes cfos and cjun after hepatic ischemia/reperfusion in rats [J]. Hepatobiliary Pancreat Dis Int， 2005; 4(2)∶197.
  19. 19. Cai FG, Xiao JS, Ye QF. Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats [J]. World J Gastroenterol， 2006; 12(18)∶2936.
  20. 20. Clavien PA, Yadav S, Sindram D, et al. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans [J]. Ann Surg， 2000; 232(2)∶155.
  21. 21. Nuzzo G, Giuliante F, Vellone M, et al. Pedicle clamping with ischemic preconditioning in liver resection [J]. Liver Transpl， 2004; 10(2 Suppl 1)∶S53.
  22. 22. 梁力建， 李紹強， 黃潔夫. 缺血預(yù)處理對肝硬化肝癌患者入肝血流阻斷肝切除的保護作用及其機理探討 [J]. 中華外科雜志, 2002; 40(4)∶265.
  23. 23. Li SQ, Liang LJ, Huang JF, et al. Ischemic preconditioning protects liver from hepatectomy under hepatic inflow occlusion for hepatocellular carcinoma patients with cirrhosis [J]. World J Gastroenterol， 2004; 10(17)∶2580.
  24. 24. Azoulay D, Lucidi V, Andreani P, et al. Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study [J]. J Am Coll Surg， 2006; 202(2)∶203.
  25. 25. 秦嵩, 孫備, 許軍, 等. 缺血預(yù)處理對大鼠肝臟低溫保存損傷的保護作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2003; 10(4)∶323.
  26. 26. Compagnon P, Lindell S, Ametani MS, et al. Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals [J]. Transplantation， 2005; 79(10)∶1393.
  27. 27. Niemann CU, Hirose R, Liu T, et al. Ischemic preconditioning improves energy state and transplantation survival in obese Zucker rat livers [J]. Anesth Analg， 2005; 101(6)∶1577.
  28. 28. Azoulay D, Del Gaudio M, Andreani P, et al. Effects of 10 minutes of ischemic preconditioning of the cadaveric liver on the graft’s preservation and function: the ying and the yang [J]. Ann Surg， 2005; 242(1)∶133.
  29. 29. Koneru B, Fisher A, He Y, et al. Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy [J]. Liver Transpl， 2005; 11(2)∶196.
  30. 30. Cescon M, Grazi GL, Grassi A, et al. Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study [J]. Liver Transpl， 2006; 12(4)∶628.
  31. 31. Kadono J, Hamada N, Fukueda M, et al. Advantage of ischemic preconditioning for hepatic resection in pigs [J]. J Surg Res， 2006; 134(2)∶173.
  32. 32. Rüdiger HA, Kang KJ, Sindram D, et al. Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver [J]. Ann Surg， 2002; 235(3)∶400.
  33. 33. Petrowsky H, McCormack L, Trujillo M, et al. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection [J]. Ann Surg， 2006; 244(6)∶921.
  34. 34. Smyrniotis V, Kostopanagiotou G, Theodoraki K, et al. Ischemic preconditioning versus intermittent vascular inflow control during major liver resection in pigs [J]. World J Surg， 2005; 29(7)∶930.
  35. 35. Eipel C, Glanemann M, Nuessler AK, et al. Ischemic preconditioning impairs liver regeneration in extended reducedsize livers [J]. Ann Surg， 2005; 241(3)∶477.