急性肝功能衰竭大動物模型研究進展_West China Medical Journal

Authors：

陳擁華 ¹ , 杜冰清 ¹ , 陸燕蓉 ² , 劉續寶 ¹ ,  麥剛 ¹

Corresponding?author：

麥剛, Email: chenyonghua2007@163.com

Keywords：

急性肝功能衰竭; 大動物模型; 肝支持系統; 肝再生

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【摘要】　急性肝功能衰竭（acute liver failure，ALF）是一種極為嚴重且進展迅速的臨床綜合癥且最具挑戰性臨床醫學問題，鑒于對ALF認識不足及對患者進行研究的困難，建立準確反映人ALF臨床特征的動物模型至關重要。目前ALF大動物模型眾多。主要應用豬、狗，通過手術方法（全肝切除、部分肝切除、肝缺血）或化學藥物方法（醋氨酚、D-氨基半乳糖、四氯化碳等）建模。然而現今的模型都不能準確地重現人ALF，都有其局限性。可喜的是兔出血病病毒模型可很好重現人ALF臨床生理、生化特征，但兔同人差異大。進一步嘗試建立大動物感染模型以及非人靈長類動物模型十分必要，且將是未來趨勢。

Citation： 陳擁華,杜冰清,陸燕蓉,劉續寶,麥剛. 急性肝功能衰竭大動物模型研究進展. West China Medical Journal, 2011, 26(2): 292-296. doi: Copy

1.	Lee WM, Squires RH Jr, Nyberg SL, et al. Acute liver failure: summary of a workshop[J]. Hepatology, 2008, 47(4): 1401-1415.
2.	Ostapowicz G, Lee WM. Acute hepatic failure: a Western perspective[J]. J Gastroenterol Hepatol, 2000, 15(5): 480-488.
3.	Auzinger G, Wendon J. Intensive care management of acute liver failure[J]. Curr Opin Crit Care, 2008, 14(2): 179-188.
4.	van de Kerkhove MP, Hoekstra R, Chamuleau RA, et al. Clinical application of bioartificial liver support systems[J]. Ann Surg, 2004, 240(2): 216-230.
5.	Nussler A, Konig S, Ott M, et al. Present status and perspectives of cell-based therapies for liver diseases[J]. J Hepatol, 2006, 45(1): 144-159.
6.	Stravitz RT. Critical management decisions in patients with acute liver failure[J]. Chest, 2008, 134(5): 1092-1102.
7.	Chiu A, Fan ST. MARS in the treatment of liver failure: Controversies and evidence[J]. Int J Artif Organs, 2006, 29(7): 660-667.
8.	Ekser B, Rigotti P, Gridelli B, et al. Xenotransplantation of solid organs in the pig-to-primate model[J]. Transpl Immunol, 2009, 21(2): 87-92.
9.	Allen JW, Hassanein T, Bhatia SN. Advances in bioartificial liver devices[J]. Hepatology, 2001, 34(3): 447-455.
10.	Li LJ, Du WB, Zhang YM, et al. Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs[J]. J Hepatol, 2006, 44(2): 317-324.
11.	Khan SA, Shah N, Williams R, et al. Acute liver failure: a review[J]. Clin Liver Dis, 2006, 10(2): 239-258.
12.	Stadbauer V, Jalan R. Acute liver failure: liver support therapies[J]. Curr Opin Crit Care, 2007, 13(2): 215-221.
13.	Jalan R. Acute liver failure: current management and future prospects[J]. J Hepatol, 2005, 42 (Suppl 1): S115-S123.
14.	Riordan SM, Williams R. Perspectives on liver failure: past and future[J]. Semin Liver Dis, 2008, 28(2): 137-141.
15.	Tunon MJ, Alvarez M, Culebras JM, et al. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure[J]. World J Gastroenterol, 2009, 15(25): 3086-3098.
16.	Terblanche J, Hickman R. Animal-models of fulminant hepatic-failure[J]. Digest Dis Sci, 1991, 36(6): 770-774.
17.	Fournea I. Potentially reversible model of acute liver failure in the pig. A model to test the efficiency of bioartificial liver[M]. Thesis: Leuven University Press, 2001: 41-56.
18.	Newsome PN, Plevris JN, Nelson LJ, et al. Animal models of fulminant hepatic failure: a critical evaluation[J]. Liver Transpl, 2000, 6(1): 21-31.
19.	O’Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure[J]. Gastroenterology, 1989, 97(2): 439-445.
20.	Rahman TM, Hodgson HJ. Animal models of acute hepatic failure[J]. Int J Exp Pathol, 2000, 81(2): 145-157.
21.	Belanger M, Butterworth RF. Acute liver failure: a critical appraisal of available animal models[J]. Metab Brain Dis, 2005, 20(4): 409-423.
22.	van de Kerkhove MP, Hoekstra R, van Gulik TM, et al. Large animal models of fulminant hepatic failure in artificial and bioartificial liver support research[J]. Biomaterials, 2004, 25(9): 1613-1625.
23.	Filipponi F, Boggi U, Meacci L, et al. A new technique for total hepatectomy in the pig for testing liver support devices[J]. Surgery, 1999, 125(4): 448-455.
24.	Sosef MN, Abrahamse LS L, van de Kerkhove MP, et al. Assessment of the AMC-bioartificial liver in the anhepatic pig[J]. Transplantation, 2002, 73(2): 204-209.
25.	Sosef MN, van Gulik TM. Total hepatectomy model in pigs: revised method for vascular reconstruction using a rigid vascular prosthesis[J]. Eur Surg Res, 2004, 36(1): 8-12.
26.	Hollestelle MJ, Poyck PP, Hollestelle JM, et al. Extra-hepatic factor Ⅷ expression in porcine fulminant hepatic failure[J]. J Thromb Haemost, 2005, 3(10): 2274-2280.
27.	Knubben K, Thiel C, Schenk M, et al. A new surgical model for hepatectomy in pigs[J]. Eur Surg Res, 2008, 40(1): 41-46.
28.	Fruhauf NR, Oldhafer KJ, Westermann S, et al. Acute hepatic failure in swine: hepatectomy versus vascular occlusion[J]. J Invest Surg, 2004, 17(3): 163-171.
29.	Filipponi F, Fabbri LP, Marsili M, et al. A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury[J]. Eur Surg Res, 1991, 23 (1): 58-64.
30.	Nardo B, Tsivian M, Neri F, et al. Extracorporeal portal vein oxygenation improves outcome of acute liver failure in swine[J]. Transpl Proceed, 2008, 40(6): 2046-2048.
31.	Chen XP, Xue YL, Li XJ, et al. Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure[J]. World J Gastroenterol, 2001, 7(5): 706-709.
32.	趙世峰, 薛毅瓏, 陳小平, 等. BioLiver-Ⅰ型生物人工肝支持系統治療兩種急性肝衰竭犬的實驗研究[J]. 解放軍醫學雜志, 2005, 30(6): 490-493.
33.	Ferko A, Plodr M, Dobes D, et al. Sharp transsection of the parenchyma in liver resection[J]. Rozhl Chir, 2003, 82(8) : 407-412.
34.	Topp SA, McClurken M, Lipson D, et al. Saline-linked surface radiofrequency ablation: factors affecting steam popping and depth of injury in the pig liver[J]. Ann Surg, 2004, 239(4): 518-527.
35.	Ladurner R, Hochleitner B, Schneeberger S, et al. Extended liver resection and hepatic ischemia in pigs: a new, potentially reversible model to induce acute liver failure and study artificial liver support systems[J]. Eur Surg Res, 2005, 37(6): 365-369.
36.	Fukueda M, Ishizaki N, Hamada N, et al. Porcine model of auxiliary partial orthotopic liver transplantation for acute liver failure[J]. Transplantation, 2006, 82(10): 1312-1318.
37.	Ytrebo LM, Nedredal GI, Langbakk B, et al. An experimental large animal model for the assessment of bioartificial liver support systems in fulminant hepatic failure[J]. Scand J Gastroenterol, 2002, 37(9): 1077-1088.
38.	Nakazawa K, Ijima H, Fukuda J, et al. Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment[J]. Int J Artif Organs, 2002, 25(1): 51-60.
39.	Kieslichova E, Ryska M, Pantoflieek T, et al. Hemodynamic parameters in a surgical devascularization model of fulmi nant hepa tic failure in the minipig[J]. Physiol Res, 2005, 54(50): 485-490.
40.	Nieuwoudt M, Kunnike R, Smuts M, et al. Standardization criteria for an ischemic surgical modelof acute hepatic failure in pigs[J]. Biomaterials, 2006, 27(20): 3836-3845.
41.	Gao Y, Mu N, Xu XP, et al. Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system[J]. World J Gastroenterol, 2005, 11(35): 5468-5474.
42.	Sen S, Rose C, Ytrebo LM, et al. Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study[J]. Crit Care Med, 2006, 34(1): 158-164.
43.	Ekse S, Clapp LH, Revhaug A, et al. Endotheliumderived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure[J]. Scand J Gastroenterol, 2007, 42(3): 356-365.
44.	Arkadopoulos N, Vlhakos D, Kostopanagiotou G, et al. Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure[J]. Liver Transpl, 2008, 14(8): 1116-1124.
45.	Rose C, Ytrebo LM, Davies NA, et al. Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure[J]. Hepatology, 2007, 46(6): 1883-1892.
46.	Yuasa T, Yamamoto T, Rivas-Carrillo JD, et al. Laparoscopy-assisted creation of a liver failure model in pigs[J]. Cell Transpl, 2008, 17(1-2): 187-193.
47.	陳鐘, 丁義濤. 犬急性肝衰竭一種新模型的建立[J]. 中國普通外科雜志, 2003, 2(3): 206-208.
48.	Chen Z, Ding YT. Functional evaluation of a new bioartificial liver system in vitro and in vitro[J]. World J Gastroenterol, 2006, 12(8): 1312-1316.
49.	Francavilla A, Makowka L, Polimeno L, et al. A dog model for acetaminophen-induced fulminant hepatic failure[J]. Gastroenterology, 1989, 96(2): 470-478.
50.	Kelly JH, Koussayer T, He DE, et al. An improved model of acetaminophen-induced fulminant hepatic failure in dogs[J]. Hepatology, 1992, 15 (2): 329-335.
51.	Sielaff TD, Hu MY, Rollins MD, et al. An anesthetized model of lethal canine galactosamine fulminant hepatic failure[J]. Hepatology, 1995, 21 (3): 796-804.
52.	Diaz-Buxo JA, Blumenthal S, Hayes D, et al. Galactosamine-induced fulminant hepatic necrosis in unanesthetized canines[J]. Hepatology, 1997, 25 (4): 950-957.
53.	Kalpana K, Ong HS, Soo KC, et al. An improved model of galactosamine-induced fulminant hepatic failure in the pig[J]. J Surg Res, 1999, 82(2): 121-130.
54.	Patzer JF, Mazariegos GV, Lopez R. Preclinical evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System[J]. J Am Coll Surg, 2002, 195 (3): 299-310.
55.	喬玲, 李亞明, 張晶, 等. 藥物性急性肝衰竭動物模型的建立[J]. 傳染病信息, 2007, 20(5): 296-298, 301.
56.	李亞明, 張晶, 趙軍, 等. 非生物型組合人工肝治療急性肝衰竭實驗研究[J]. 中國實用內科雜志, 2006, 26(24): 1947-1949.
57.	Zhang F, He YW, Duan ZP. Changes of high mobility group box 1 in serum of pig acute hepatic failure model and significance[J]. J Huazhong Univ Sci Technolog Med Sci, 2008, 28(1): 52-55.
58.	彭承宏, 肖衛東, 吳傳頂, 等. 門靜脈注射氨基半乳糖和脂多糖建立豬急性肝功能衰竭模型[J]. 中華醫學雜志, 2005, 85(21): 1464-1467.
59.	肖衛東, 彭承宏. 李勇, 等. 肝移植治療豬急性肝功能衰竭的近期療效和手術體會[J]. 肝膽外科志, 2006, 14(2): 140-142.
60.	禤文海, 胡以則, 彭和平, 等. 犬暴發性肝功能衰竭模型的建立[J]. 中國普通外科雜志, 2002, 11(9): 548-550.
61.	Ishiguro S, Takada Y, Gu M, et al. Auxiliary partial orthotopic liver transplantation for fulminant hepatitis: regeneration of the diseased native iver in a pig model[J]. Transplantation, 2003, 75(11): 1901-1904.
62.	Ishizawa Y, Totsuka E, Umehara M, et al. Efficacy of double-filtration plasmapheretic cross-circulation with a high-permeability membrane using canine harvested liver in porcine fulminant hepatic failure model[J]. Transpl Proceed, 2004, 36(8): 2344-2348.
63.	Tunon MJ, Sanchez-Campos S, Garcia-Ferreras J, et al. Rabbit hemorrhagic viral disease: characterization of a new animal model of fulminant liver failure[J]. J Lab Clin Med, 2003, 141(4): 272-278.
64.	San-Miguel B, Alvarez M, Culebras JM, et al. N-acetyl-cysteine protects liver from apoptotic death in an animal model of fulminant hepatic failure[J]. Apoptosis, 2006, 11(11): 1945-1957.

1. 　Lee WM, Squires RH Jr, Nyberg SL, et al. Acute liver failure: summary of a workshop[J]. Hepatology, 2008, 47(4): 1401-1415.
2. 　Ostapowicz G, Lee WM. Acute hepatic failure: a Western perspective[J]. J Gastroenterol Hepatol, 2000, 15(5): 480-488.
3. 　Auzinger G, Wendon J. Intensive care management of acute liver failure[J]. Curr Opin Crit Care, 2008, 14(2): 179-188.
4. 　van de Kerkhove MP, Hoekstra R, Chamuleau RA, et al. Clinical application of bioartificial liver support systems[J]. Ann Surg, 2004, 240(2): 216-230.
5. 　Nussler A, Konig S, Ott M, et al. Present status and perspectives of cell-based therapies for liver diseases[J]. J Hepatol, 2006, 45(1): 144-159.
6. 　Stravitz RT. Critical management decisions in patients with acute liver failure[J]. Chest, 2008, 134(5): 1092-1102.
7. 　Chiu A, Fan ST. MARS in the treatment of liver failure: Controversies and evidence[J]. Int J Artif Organs, 2006, 29(7): 660-667.
8. 　Ekser B, Rigotti P, Gridelli B, et al. Xenotransplantation of solid organs in the pig-to-primate model[J]. Transpl Immunol, 2009, 21(2): 87-92.
9. 　Allen JW, Hassanein T, Bhatia SN. Advances in bioartificial liver devices[J]. Hepatology, 2001, 34(3): 447-455.
10. 　Li LJ, Du WB, Zhang YM, et al. Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs[J]. J Hepatol, 2006, 44(2): 317-324.
11. 　Khan SA, Shah N, Williams R, et al. Acute liver failure: a review[J]. Clin Liver Dis, 2006, 10(2): 239-258.
12. 　Stadbauer V, Jalan R. Acute liver failure: liver support therapies[J]. Curr Opin Crit Care, 2007, 13(2): 215-221.
13. 　Jalan R. Acute liver failure: current management and future prospects[J]. J Hepatol, 2005, 42 (Suppl 1): S115-S123.
14. 　Riordan SM, Williams R. Perspectives on liver failure: past and future[J]. Semin Liver Dis, 2008, 28(2): 137-141.
15. 　Tunon MJ, Alvarez M, Culebras JM, et al. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure[J]. World J Gastroenterol, 2009, 15(25): 3086-3098.
16. 　Terblanche J, Hickman R. Animal-models of fulminant hepatic-failure[J]. Digest Dis Sci, 1991, 36(6): 770-774.
17. 　Fournea I. Potentially reversible model of acute liver failure in the pig. A model to test the efficiency of bioartificial liver[M]. Thesis: Leuven University Press, 2001: 41-56.
18. 　Newsome PN, Plevris JN, Nelson LJ, et al. Animal models of fulminant hepatic failure: a critical evaluation[J]. Liver Transpl, 2000, 6(1): 21-31.
19. 　O’Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure[J]. Gastroenterology, 1989, 97(2): 439-445.
20. 　Rahman TM, Hodgson HJ. Animal models of acute hepatic failure[J]. Int J Exp Pathol, 2000, 81(2): 145-157.
21. 　Belanger M, Butterworth RF. Acute liver failure: a critical appraisal of available animal models[J]. Metab Brain Dis, 2005, 20(4): 409-423.
22. 　van de Kerkhove MP, Hoekstra R, van Gulik TM, et al. Large animal models of fulminant hepatic failure in artificial and bioartificial liver support research[J]. Biomaterials, 2004, 25(9): 1613-1625.
23. 　Filipponi F, Boggi U, Meacci L, et al. A new technique for total hepatectomy in the pig for testing liver support devices[J]. Surgery, 1999, 125(4): 448-455.
24. 　Sosef MN, Abrahamse LS L, van de Kerkhove MP, et al. Assessment of the AMC-bioartificial liver in the anhepatic pig[J]. Transplantation, 2002, 73(2): 204-209.
25. 　Sosef MN, van Gulik TM. Total hepatectomy model in pigs: revised method for vascular reconstruction using a rigid vascular prosthesis[J]. Eur Surg Res, 2004, 36(1): 8-12.
26. 　Hollestelle MJ, Poyck PP, Hollestelle JM, et al. Extra-hepatic factor Ⅷ expression in porcine fulminant hepatic failure[J]. J Thromb Haemost, 2005, 3(10): 2274-2280.
27. 　Knubben K, Thiel C, Schenk M, et al. A new surgical model for hepatectomy in pigs[J]. Eur Surg Res, 2008, 40(1): 41-46.
28. 　Fruhauf NR, Oldhafer KJ, Westermann S, et al. Acute hepatic failure in swine: hepatectomy versus vascular occlusion[J]. J Invest Surg, 2004, 17(3): 163-171.
29. 　Filipponi F, Fabbri LP, Marsili M, et al. A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury[J]. Eur Surg Res, 1991, 23 (1): 58-64.
30. 　Nardo B, Tsivian M, Neri F, et al. Extracorporeal portal vein oxygenation improves outcome of acute liver failure in swine[J]. Transpl Proceed, 2008, 40(6): 2046-2048.
31. 　Chen XP, Xue YL, Li XJ, et al. Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure[J]. World J Gastroenterol, 2001, 7(5): 706-709.
32. 　趙世峰, 薛毅瓏, 陳小平, 等. BioLiver-Ⅰ型生物人工肝支持系統治療兩種急性肝衰竭犬的實驗研究[J]. 解放軍醫學雜志, 2005, 30(6): 490-493.
33. 　Ferko A, Plodr M, Dobes D, et al. Sharp transsection of the parenchyma in liver resection[J]. Rozhl Chir, 2003, 82(8) : 407-412.
34. 　Topp SA, McClurken M, Lipson D, et al. Saline-linked surface radiofrequency ablation: factors affecting steam popping and depth of injury in the pig liver[J]. Ann Surg, 2004, 239(4): 518-527.
35. 　Ladurner R, Hochleitner B, Schneeberger S, et al. Extended liver resection and hepatic ischemia in pigs: a new, potentially reversible model to induce acute liver failure and study artificial liver support systems[J]. Eur Surg Res, 2005, 37(6): 365-369.
36. 　Fukueda M, Ishizaki N, Hamada N, et al. Porcine model of auxiliary partial orthotopic liver transplantation for acute liver failure[J]. Transplantation, 2006, 82(10): 1312-1318.
37. 　Ytrebo LM, Nedredal GI, Langbakk B, et al. An experimental large animal model for the assessment of bioartificial liver support systems in fulminant hepatic failure[J]. Scand J Gastroenterol, 2002, 37(9): 1077-1088.
38. 　Nakazawa K, Ijima H, Fukuda J, et al. Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment[J]. Int J Artif Organs, 2002, 25(1): 51-60.
39. 　Kieslichova E, Ryska M, Pantoflieek T, et al. Hemodynamic parameters in a surgical devascularization model of fulmi nant hepa tic failure in the minipig[J]. Physiol Res, 2005, 54(50): 485-490.
40. 　Nieuwoudt M, Kunnike R, Smuts M, et al. Standardization criteria for an ischemic surgical modelof acute hepatic failure in pigs[J]. Biomaterials, 2006, 27(20): 3836-3845.
41. 　Gao Y, Mu N, Xu XP, et al. Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system[J]. World J Gastroenterol, 2005, 11(35): 5468-5474.
42. 　Sen S, Rose C, Ytrebo LM, et al. Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study[J]. Crit Care Med, 2006, 34(1): 158-164.
43. 　Ekse S, Clapp LH, Revhaug A, et al. Endotheliumderived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure[J]. Scand J Gastroenterol, 2007, 42(3): 356-365.
44. 　Arkadopoulos N, Vlhakos D, Kostopanagiotou G, et al. Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure[J]. Liver Transpl, 2008, 14(8): 1116-1124.
45. 　Rose C, Ytrebo LM, Davies NA, et al. Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure[J]. Hepatology, 2007, 46(6): 1883-1892.
46. 　Yuasa T, Yamamoto T, Rivas-Carrillo JD, et al. Laparoscopy-assisted creation of a liver failure model in pigs[J]. Cell Transpl, 2008, 17(1-2): 187-193.
47. 　陳鐘, 丁義濤. 犬急性肝衰竭一種新模型的建立[J]. 中國普通外科雜志, 2003, 2(3): 206-208.
48. 　Chen Z, Ding YT. Functional evaluation of a new bioartificial liver system in vitro and in vitro[J]. World J Gastroenterol, 2006, 12(8): 1312-1316.
49. 　Francavilla A, Makowka L, Polimeno L, et al. A dog model for acetaminophen-induced fulminant hepatic failure[J]. Gastroenterology, 1989, 96(2): 470-478.
50. 　Kelly JH, Koussayer T, He DE, et al. An improved model of acetaminophen-induced fulminant hepatic failure in dogs[J]. Hepatology, 1992, 15 (2): 329-335.
51. 　Sielaff TD, Hu MY, Rollins MD, et al. An anesthetized model of lethal canine galactosamine fulminant hepatic failure[J]. Hepatology, 1995, 21 (3): 796-804.
52. 　Diaz-Buxo JA, Blumenthal S, Hayes D, et al. Galactosamine-induced fulminant hepatic necrosis in unanesthetized canines[J]. Hepatology, 1997, 25 (4): 950-957.
53. 　Kalpana K, Ong HS, Soo KC, et al. An improved model of galactosamine-induced fulminant hepatic failure in the pig[J]. J Surg Res, 1999, 82(2): 121-130.
54. 　Patzer JF, Mazariegos GV, Lopez R. Preclinical evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System[J]. J Am Coll Surg, 2002, 195 (3): 299-310.
55. 　喬玲, 李亞明, 張晶, 等. 藥物性急性肝衰竭動物模型的建立[J]. 傳染病信息, 2007, 20(5): 296-298, 301.
56. 　李亞明, 張晶, 趙軍, 等. 非生物型組合人工肝治療急性肝衰竭實驗研究[J]. 中國實用內科雜志, 2006, 26(24): 1947-1949.
57. 　Zhang F, He YW, Duan ZP. Changes of high mobility group box 1 in serum of pig acute hepatic failure model and significance[J]. J Huazhong Univ Sci Technolog Med Sci, 2008, 28(1): 52-55.
58. 　彭承宏, 肖衛東, 吳傳頂, 等. 門靜脈注射氨基半乳糖和脂多糖建立豬急性肝功能衰竭模型[J]. 中華醫學雜志, 2005, 85(21): 1464-1467.
59. 　肖衛東, 彭承宏. 李勇, 等. 肝移植治療豬急性肝功能衰竭的近期療效和手術體會[J]. 肝膽外科志, 2006, 14(2): 140-142.
60. 　禤文海, 胡以則, 彭和平, 等. 犬暴發性肝功能衰竭模型的建立[J]. 中國普通外科雜志, 2002, 11(9): 548-550.
61. 　Ishiguro S, Takada Y, Gu M, et al. Auxiliary partial orthotopic liver transplantation for fulminant hepatitis: regeneration of the diseased native iver in a pig model[J]. Transplantation, 2003, 75(11): 1901-1904.
62. 　Ishizawa Y, Totsuka E, Umehara M, et al. Efficacy of double-filtration plasmapheretic cross-circulation with a high-permeability membrane using canine harvested liver in porcine fulminant hepatic failure model[J]. Transpl Proceed, 2004, 36(8): 2344-2348.
63. 　Tunon MJ, Sanchez-Campos S, Garcia-Ferreras J, et al. Rabbit hemorrhagic viral disease: characterization of a new animal model of fulminant liver failure[J]. J Lab Clin Med, 2003, 141(4): 272-278.
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West China Medical Journal

急性肝功能衰竭大動物模型研究進展

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