• 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(hù)機(jī)理及其在肝切除、肝移植中的臨床研究進(jìn)展。方法:復(fù)習(xí)近年來(lái)肝臟IPC的基礎(chǔ)和臨床研究的文獻(xiàn)。 ]
結(jié)果:實(shí)驗(yàn)研究表明，IPC主要通過(guò)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(guò)氧化和氧自由基的產(chǎn)生、抑制炎性細(xì)胞的激活和細(xì)胞因子的釋放、抑制細(xì)胞凋亡、誘導(dǎo)內(nèi)源性保護(hù)物質(zhì)的釋放等途徑保護(hù)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(hù)作用，但也有報(bào)道顯示IPC不能保護(hù)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(jià)值有待進(jìn)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(jìn)展. 中國(guó)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(ài)華， 等. 缺血預(yù)處理對(duì)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(guó)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(guó)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(qiáng)， 黃潔夫. 缺血預(yù)處理對(duì)肝硬化肝癌患者入肝血流阻斷肝切除的保護(hù)作用及其機(jī)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(duì)大鼠肝臟低溫保存損傷的保護(hù)作用 [J]. 中國(guó)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(ài)華， 等. 缺血預(yù)處理對(duì)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(guó)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(guó)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(qiáng)， 黃潔夫. 缺血預(yù)處理對(duì)肝硬化肝癌患者入肝血流阻斷肝切除的保護(hù)作用及其機(jī)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(duì)大鼠肝臟低溫保存損傷的保護(hù)作用 [J]. 中國(guó)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.