小鼠实验性肝损伤模型的研究进展
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摘要
针对实验目的不同选择合适的小鼠肝损伤动物模型对于临床上肝病的防治、发病机制的研究和护肝药物的筛选都有着重要意义。依据国内外参考文献将肝损伤小鼠模型归纳为化学性、药物性、免疫性、酒精性、肝部分切除术等几类。以小鼠肝损伤动物模型分类为切入点,对其发病机制、药物剂量、成模时间、适用范围及优缺点进行综述,以期为小鼠实验性肝损伤模型的选择提供一个参考。
To select the appropriate mouse model of liver injury is of great significance for the research on prevention and treatment of liver disease,the study of its pathogenesis and the screening of drugs to protect the liver.According to references published internationally, mouse models of liver injury were classified into chemical,pharmacological,immunological,alcoholic,and partial hepatectomy studies. Based on the classification of models of liver injury in mice,the pathogenesis,dosage of drugs,time of model formation,applicable scope,and advantages and disadvantages were reviewed to provide a reference for the selection of experimental mouse liver injury models.
To select the appropriate mouse model of liver injury is of great significance for the research on prevention and treatment of liver disease,the study of its pathogenesis and the screening of drugs to protect the liver.According to references published internationally, mouse models of liver injury were classified into chemical,pharmacological,immunological,alcoholic,and partial hepatectomy studies. Based on the classification of models of liver injury in mice,the pathogenesis,dosage of drugs,time of model formation,applicable scope,and advantages and disadvantages were reviewed to provide a reference for the selection of experimental mouse liver injury models.
引文
[1] Lee IC,Kim SH,Baek HS,et al. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachlorideinduced hepatic oxidative damage and inflammatory response in rats[J]. Food Chem Toxicol,2014,63:174-185.
[2] Su C,Xia X,Shi Q,et al. Neohesperidin dihydrochalcone versus CCl4-induced hepatic injury through different mechanisms:the implication of free radical scavenging and Nrf2activation[J]. J Agric Food Chem,2015,63(22):5468-5475.
[3] Wang M,Zhang XJ,Feng R,et al. Hepatoprotective properties of Penthorum chinense Pursh against carbon tetrachloride-induced acute liver injury in mice[J]. Chin Med,2017,12:32.
[4]李梦,翟亚南,王晶晶,等.制备低剂量四氯化碳诱导小鼠慢性肝损伤模型的探讨[J].中国实验动物学报,2014,22(4):52-55.
[5]周琼,刘芳萍,刘颖姝,等.四氯化碳致小鼠急性肝损伤动物模型建立方法的研究[J].东北农业大学学报,2012,43(6):77-81.
[6] Mei H,Ying L,Liu M,et al. Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat[J]. BMC Nephrol,2012,13:25.
[7] Liu XY,Robinson D,Veach RA,et al. Peptide-directed suppression of a pro-inflammatory cytokine response[J]. J Biol Chem,2000,275(22):16774-16778.
[8] Yang F,Li X,Wang LK,et al. Inhibitions of NF-κB and TNF-αresult in differential effects in rats with acute on chronic liver failure induced by d-Gal and LPS[J]. Inflammation,2014,37(3):848-857.
[9] Lian LH,Wu YL,Wan Y,et al. Anti-apoptotic activity of gentiopicroside in d-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure[J]. Chem Biol Interact,2010,188(1):127-133.
[10] Shin JW,Jing HW,Park HJ,et al. Herbal formula CGX ameliorates LPS/d-galactosamine-induced hepatitis[J]. Food Chem Toxicol,2011,49(6):1329-1334.
[11] Furuya S,Kono H,Hara M,et al. Interleukin 17A plays a role in lipopolysaccharide/d-galactosamine-induced fulminant hepatic injury in mice[J]. J Surg Res,2015,199(2):487-493.
[12]吴小红,郭彦,刘晨风,等. LPS/D-GalN诱导小鼠急性肝损伤模型的建立[J].中国实验动物学报,2014,22(3):15-19.
[13] Zhang Q,Yang F,Li X,et al. Trichostatin A protects against experimental acute-on-chronic liver failure in rats through regulating the acetylation of nuclear factor-κB[J].Inflammation,2015,38(3):1364-1373.
[14] Syed I,Rathod J,Parmar M,et al. Matrix metalloproteinase-9,-10,and-12,MDM2 and p53 expression in mouse liver during dimethylnitrosamine-induced oxidative stress and genomic injury[J]. Mol Cell Biochem,2012,365(1-2):351-361.
[15] Svegliati-Baroni G,Saccomanno S,Goor H,et al. Involvement of reactive oxygen species and nitric oxide radicals in activation and proliferation of rat hepatic stellate cells[J]. Liver,2001,21(1):1-12.
[16] Amirtharaj GJ,Thangaraj KR,Kini A,et al. Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow[J]. Toxicol Rep,2014,1:707-717.
[17]张玲,江远,何金洋,等.二甲基亚硝胺诱导小鼠肝损伤模型的建立及其机制研究[J].中西医结合肝病杂志,2010,20(4):228-230.
[18] Palmeira CM,Rolo AP. Mitochondrially-mediated toxicity of bile acids[J]. Toxicology,2004,203(1-3):1-15.
[19] Dietrich CG,Ottenhoff R,de Waart DR,et al. Role of MRP2and GSH in intrahepatic cycling of toxins[J]. Toxicology,2001,167(1):73-81.
[20] Zidek N,Hellmann J,Kramer PJ,et al. Acute hepatotoxicity:a predictive model based on focused illumina microarrays[J].Toxicol Sci,2007,99(1):289-302.
[21] Cullen JM,Faiola B,Melich DH,et al. Effects of Kupffer cell depletion on acute alpha-naphthylisothiocyanate-induced liver toxicity in male mice[J]. Toxicol Pathol,2013,41(1):7-17.
[22] Corbalan R, Chatauret NS, Butterworth RF, et al. Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients[J]. Hepatology,2002,36(5):1155-1162.
[23] Wang H,Zhang H,Zhang Y,et al. Plumbagin protects liver against fulminant hepatic failure and chronic liver fibrosis via inhibiting inflammation and collagen production[J]. Oncotarget,2016,7(50):82864-82875.
[24] Larsen FS,Wendon J. Understanding paracetamol-induced liver failure[J]. Intensive Care Med,2014,40(6):888-890.
[25] Mossanen JC,Tacke F. Acetaminophen-induced acute liver injury in mice[J]. Lab Anim,2015,49(1 Suppl):30-36.
[26] Bachmann M,Pfeilschifter J,Mühl H. A prominent role of interleukin-18 in acetaminophen-induced liver injury advocates its blockage for therapy of hepatic necroinflammation[J]. Front Immunol,2018,9:161.
[27] Bhushan B,Walesky C,Manley M,et al. Pro-regenerative signaling after acetaminophen-induced acute liver injury in mice identified using a novel incremental dose model[J]. Am J Pathol,2014,184(11):3013-3025.
[28] Sarich TC,Adams SP,Petricca G,et al. Inhibition of isoniazidinduced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor[J]. J Pharmacol Exp Ther,1999,289(2):695-702.
[29] Sarich TC,Youssefi M,Zhou T,et al. Role of hydrazine in the mechanism of isoniazid hepatotoxicity in rabbits[J]. Arch Toxicol,1996,70(12):835-840.
[30] Jenner AM,Timbrell JA. Influence of inducers and inhibitors of cytochrome P450 on the hepatotoxicity of hydrazine in vivo[J].Arch Toxicol,1994,68(6):349-357.
[31] Chowdhury A,Santra A,Bhattacharjee K,et al. Mitochondrial oxidative stress and permeability transition in isoniazid and rifampicin induced liver injury in mice[J]. J Hepatol,2006,45(1):117-126.
[32] Chen X, Xu J, Zhang C, et al. The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice[J]. Eur J Pharmacol,2011,659(1):53-60.
[33] Enriquezcortina C,Almontebecerril M,Clavijocornejo D,et al.Hepatocyte growth factor protects against isoniazid/rifampicininduced oxidative liver damage[J]. Toxicol Sci,2013,135(1):26-36.
[34] Gallelli L,Staltari O,Palleria C,et al. Hepatotoxicity induced by methimazole in a previously healthy patient[J]. Curr Drug Saf,2009,4(3):204-206.
[35] Heidari R,Niknahad H,Jamshidzadeh A,et al. Factors affecting drug-induced liver injury:antithyroid drugs as instances[J].Clin Mol Hepatol,2014,20(3):237-248.
[36] Kobayashi M,Higuchi S,Ide M,et al. Th2 cytokine-mediated methimazole-induced acute liver injury in mice[J]. J Appl Toxicol,2012,32(10):823-833.
[37] Chen K,Li J,Wang J,et al. 15-Deoxy-γ12,14-prostaglandin J2 reduces liver impairment in a model of ConA-induced acute hepatic inflammation by activation of PPARγand reduction in NF-κB activity[J]. PPAR Res,2014,2014:215631.
[38] He GW,Günther C,Kremer AE,et al. PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury[J].Gut,2017,66(4):716-723.
[39] Chen K,Li J,Li S,et al. 15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy[J]. Biomed Pharmacother,2016,80:183-192.
[40] Yang YF,Tan DM,Xie YT, et al. Mycophenolate mofetil prevents lethal acute liver failure in mice induced by bacille Calmette-Guerin and lipopolysaccharide[J]. J Gastroenterol Hepatol,2008,23(4):611-618.
[41] Liang Y,Zhou Y,Shen P. NF-κB and its regulation on the immune system[J].Cell Mol Immunol,2004,1(5):343-350.
[42] Guler R,Olleros ML,Vesin D,et al. Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins[J]. J Hepatol,2004,41(5):773-781.
[43] Zhang NN,Huang NY,Zhou XK,et al. Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice[J]. Inflamm Res,2012,61(1):17-26.
[44] Lu JW,Wang H,Ji YL,et al. Differential effects of pyrrolidine dithiocarbamate on TNF-α-mediated liver injury in two different models of fulminant hepatitis[J]. J Hepatol,2008,48(3):442-452.
[45] Wang S,Pacher P,Lisle RCD,et al. A mechanistic review of cell death in alcohol-induced liver injury[J]. Alcohol Clin Exp Res,2016,40(6):1215-1223.
[46] Song Y,Li N,Gu J,et al.β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway[J]. J Dairy Sci,2016,99(11):9184-9198.
[47] You M,Liang X,Ajmo JM,et al. Involvement of mammalian sirtuin 1 in the action of ethanol in the liver[J]. Am J Physiol Gastrointest Liver Physiol,2008,294(4):G892-G898.
[48] Hou X,Xu S,Maitland-Toolan KA,et al. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase[J]. J Biol Chem,2008,283(29):20015-20026.
[49] You M,Jogasuria A,Taylor C,et al. Sirtuin 1 signaling and alcoholic fatty liver disease[J]. Hepatobiliary Surg Nutr,2015,4(2):88-100.
[50] Li Y,Xu S,Mihaylova M,et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin resistant mice[J]. Cell Metab,2011,13(4):376-388.
[51] Park HY,Choi HD,Eom H,et al. Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease[J]. Food Chem,2013,139(1-4):231-240.
[52]肖娟,张瑞芬,黄菲,等.两种不同的酒精摄入方式诱导的小鼠酒精性肝损伤模型比较[J].中国比较医学杂志,2016,26(6):11-17.
[53] Sharda DR,Millerlee JL,Kanski GM,et al. Comparison of the agar block and Lieber-De Carli diets to study chronic alcohol consumption in an aging model of Fischer 344 female rats[J]. J Pharmacol Toxicol Methods,2012,66(3):257-263.
[54] Hao F,Cubero FJ,Ramadori P,et al. Inhibition of Caspase-8does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice[J]. Cell Death Dis,2017,8(10):e3152.
[55] Fausto N,Campbell JS,Riehle KJ. Liver regeneration[J]. J Hepatol,2012,57(3):692-694.
[56]雷达鑫,卜雯婧,刘贤,等. T细胞缺陷裸小鼠部分肝切除肝再生异常[J].军事医学,2017,41(6):424-429.
[57]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊治指南(2012年版)[J].中华肝脏病杂志,2013,21(3):210-216.
[58] Guo WN,Zhu B,Ai L,et al. Animal models for the study of hepatitis B virus infection[J]. Zool Res,2018,39(1):25-31.
[2] Su C,Xia X,Shi Q,et al. Neohesperidin dihydrochalcone versus CCl4-induced hepatic injury through different mechanisms:the implication of free radical scavenging and Nrf2activation[J]. J Agric Food Chem,2015,63(22):5468-5475.
[3] Wang M,Zhang XJ,Feng R,et al. Hepatoprotective properties of Penthorum chinense Pursh against carbon tetrachloride-induced acute liver injury in mice[J]. Chin Med,2017,12:32.
[4]李梦,翟亚南,王晶晶,等.制备低剂量四氯化碳诱导小鼠慢性肝损伤模型的探讨[J].中国实验动物学报,2014,22(4):52-55.
[5]周琼,刘芳萍,刘颖姝,等.四氯化碳致小鼠急性肝损伤动物模型建立方法的研究[J].东北农业大学学报,2012,43(6):77-81.
[6] Mei H,Ying L,Liu M,et al. Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat[J]. BMC Nephrol,2012,13:25.
[7] Liu XY,Robinson D,Veach RA,et al. Peptide-directed suppression of a pro-inflammatory cytokine response[J]. J Biol Chem,2000,275(22):16774-16778.
[8] Yang F,Li X,Wang LK,et al. Inhibitions of NF-κB and TNF-αresult in differential effects in rats with acute on chronic liver failure induced by d-Gal and LPS[J]. Inflammation,2014,37(3):848-857.
[9] Lian LH,Wu YL,Wan Y,et al. Anti-apoptotic activity of gentiopicroside in d-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure[J]. Chem Biol Interact,2010,188(1):127-133.
[10] Shin JW,Jing HW,Park HJ,et al. Herbal formula CGX ameliorates LPS/d-galactosamine-induced hepatitis[J]. Food Chem Toxicol,2011,49(6):1329-1334.
[11] Furuya S,Kono H,Hara M,et al. Interleukin 17A plays a role in lipopolysaccharide/d-galactosamine-induced fulminant hepatic injury in mice[J]. J Surg Res,2015,199(2):487-493.
[12]吴小红,郭彦,刘晨风,等. LPS/D-GalN诱导小鼠急性肝损伤模型的建立[J].中国实验动物学报,2014,22(3):15-19.
[13] Zhang Q,Yang F,Li X,et al. Trichostatin A protects against experimental acute-on-chronic liver failure in rats through regulating the acetylation of nuclear factor-κB[J].Inflammation,2015,38(3):1364-1373.
[14] Syed I,Rathod J,Parmar M,et al. Matrix metalloproteinase-9,-10,and-12,MDM2 and p53 expression in mouse liver during dimethylnitrosamine-induced oxidative stress and genomic injury[J]. Mol Cell Biochem,2012,365(1-2):351-361.
[15] Svegliati-Baroni G,Saccomanno S,Goor H,et al. Involvement of reactive oxygen species and nitric oxide radicals in activation and proliferation of rat hepatic stellate cells[J]. Liver,2001,21(1):1-12.
[16] Amirtharaj GJ,Thangaraj KR,Kini A,et al. Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow[J]. Toxicol Rep,2014,1:707-717.
[17]张玲,江远,何金洋,等.二甲基亚硝胺诱导小鼠肝损伤模型的建立及其机制研究[J].中西医结合肝病杂志,2010,20(4):228-230.
[18] Palmeira CM,Rolo AP. Mitochondrially-mediated toxicity of bile acids[J]. Toxicology,2004,203(1-3):1-15.
[19] Dietrich CG,Ottenhoff R,de Waart DR,et al. Role of MRP2and GSH in intrahepatic cycling of toxins[J]. Toxicology,2001,167(1):73-81.
[20] Zidek N,Hellmann J,Kramer PJ,et al. Acute hepatotoxicity:a predictive model based on focused illumina microarrays[J].Toxicol Sci,2007,99(1):289-302.
[21] Cullen JM,Faiola B,Melich DH,et al. Effects of Kupffer cell depletion on acute alpha-naphthylisothiocyanate-induced liver toxicity in male mice[J]. Toxicol Pathol,2013,41(1):7-17.
[22] Corbalan R, Chatauret NS, Butterworth RF, et al. Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients[J]. Hepatology,2002,36(5):1155-1162.
[23] Wang H,Zhang H,Zhang Y,et al. Plumbagin protects liver against fulminant hepatic failure and chronic liver fibrosis via inhibiting inflammation and collagen production[J]. Oncotarget,2016,7(50):82864-82875.
[24] Larsen FS,Wendon J. Understanding paracetamol-induced liver failure[J]. Intensive Care Med,2014,40(6):888-890.
[25] Mossanen JC,Tacke F. Acetaminophen-induced acute liver injury in mice[J]. Lab Anim,2015,49(1 Suppl):30-36.
[26] Bachmann M,Pfeilschifter J,Mühl H. A prominent role of interleukin-18 in acetaminophen-induced liver injury advocates its blockage for therapy of hepatic necroinflammation[J]. Front Immunol,2018,9:161.
[27] Bhushan B,Walesky C,Manley M,et al. Pro-regenerative signaling after acetaminophen-induced acute liver injury in mice identified using a novel incremental dose model[J]. Am J Pathol,2014,184(11):3013-3025.
[28] Sarich TC,Adams SP,Petricca G,et al. Inhibition of isoniazidinduced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor[J]. J Pharmacol Exp Ther,1999,289(2):695-702.
[29] Sarich TC,Youssefi M,Zhou T,et al. Role of hydrazine in the mechanism of isoniazid hepatotoxicity in rabbits[J]. Arch Toxicol,1996,70(12):835-840.
[30] Jenner AM,Timbrell JA. Influence of inducers and inhibitors of cytochrome P450 on the hepatotoxicity of hydrazine in vivo[J].Arch Toxicol,1994,68(6):349-357.
[31] Chowdhury A,Santra A,Bhattacharjee K,et al. Mitochondrial oxidative stress and permeability transition in isoniazid and rifampicin induced liver injury in mice[J]. J Hepatol,2006,45(1):117-126.
[32] Chen X, Xu J, Zhang C, et al. The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice[J]. Eur J Pharmacol,2011,659(1):53-60.
[33] Enriquezcortina C,Almontebecerril M,Clavijocornejo D,et al.Hepatocyte growth factor protects against isoniazid/rifampicininduced oxidative liver damage[J]. Toxicol Sci,2013,135(1):26-36.
[34] Gallelli L,Staltari O,Palleria C,et al. Hepatotoxicity induced by methimazole in a previously healthy patient[J]. Curr Drug Saf,2009,4(3):204-206.
[35] Heidari R,Niknahad H,Jamshidzadeh A,et al. Factors affecting drug-induced liver injury:antithyroid drugs as instances[J].Clin Mol Hepatol,2014,20(3):237-248.
[36] Kobayashi M,Higuchi S,Ide M,et al. Th2 cytokine-mediated methimazole-induced acute liver injury in mice[J]. J Appl Toxicol,2012,32(10):823-833.
[37] Chen K,Li J,Wang J,et al. 15-Deoxy-γ12,14-prostaglandin J2 reduces liver impairment in a model of ConA-induced acute hepatic inflammation by activation of PPARγand reduction in NF-κB activity[J]. PPAR Res,2014,2014:215631.
[38] He GW,Günther C,Kremer AE,et al. PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury[J].Gut,2017,66(4):716-723.
[39] Chen K,Li J,Li S,et al. 15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy[J]. Biomed Pharmacother,2016,80:183-192.
[40] Yang YF,Tan DM,Xie YT, et al. Mycophenolate mofetil prevents lethal acute liver failure in mice induced by bacille Calmette-Guerin and lipopolysaccharide[J]. J Gastroenterol Hepatol,2008,23(4):611-618.
[41] Liang Y,Zhou Y,Shen P. NF-κB and its regulation on the immune system[J].Cell Mol Immunol,2004,1(5):343-350.
[42] Guler R,Olleros ML,Vesin D,et al. Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins[J]. J Hepatol,2004,41(5):773-781.
[43] Zhang NN,Huang NY,Zhou XK,et al. Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice[J]. Inflamm Res,2012,61(1):17-26.
[44] Lu JW,Wang H,Ji YL,et al. Differential effects of pyrrolidine dithiocarbamate on TNF-α-mediated liver injury in two different models of fulminant hepatitis[J]. J Hepatol,2008,48(3):442-452.
[45] Wang S,Pacher P,Lisle RCD,et al. A mechanistic review of cell death in alcohol-induced liver injury[J]. Alcohol Clin Exp Res,2016,40(6):1215-1223.
[46] Song Y,Li N,Gu J,et al.β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway[J]. J Dairy Sci,2016,99(11):9184-9198.
[47] You M,Liang X,Ajmo JM,et al. Involvement of mammalian sirtuin 1 in the action of ethanol in the liver[J]. Am J Physiol Gastrointest Liver Physiol,2008,294(4):G892-G898.
[48] Hou X,Xu S,Maitland-Toolan KA,et al. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase[J]. J Biol Chem,2008,283(29):20015-20026.
[49] You M,Jogasuria A,Taylor C,et al. Sirtuin 1 signaling and alcoholic fatty liver disease[J]. Hepatobiliary Surg Nutr,2015,4(2):88-100.
[50] Li Y,Xu S,Mihaylova M,et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin resistant mice[J]. Cell Metab,2011,13(4):376-388.
[51] Park HY,Choi HD,Eom H,et al. Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease[J]. Food Chem,2013,139(1-4):231-240.
[52]肖娟,张瑞芬,黄菲,等.两种不同的酒精摄入方式诱导的小鼠酒精性肝损伤模型比较[J].中国比较医学杂志,2016,26(6):11-17.
[53] Sharda DR,Millerlee JL,Kanski GM,et al. Comparison of the agar block and Lieber-De Carli diets to study chronic alcohol consumption in an aging model of Fischer 344 female rats[J]. J Pharmacol Toxicol Methods,2012,66(3):257-263.
[54] Hao F,Cubero FJ,Ramadori P,et al. Inhibition of Caspase-8does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice[J]. Cell Death Dis,2017,8(10):e3152.
[55] Fausto N,Campbell JS,Riehle KJ. Liver regeneration[J]. J Hepatol,2012,57(3):692-694.
[56]雷达鑫,卜雯婧,刘贤,等. T细胞缺陷裸小鼠部分肝切除肝再生异常[J].军事医学,2017,41(6):424-429.
[57]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊治指南(2012年版)[J].中华肝脏病杂志,2013,21(3):210-216.
[58] Guo WN,Zhu B,Ai L,et al. Animal models for the study of hepatitis B virus infection[J]. Zool Res,2018,39(1):25-31.