Sweroside ameliorates α-naphthylisothiocyanate induced cholestatic liver injury through bile acid regulation and further pro-inflammatory responses mediation
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- 英文论文题名：Sweroside ameliorates α-naphthylisothiocyanate induced cholestatic liver injury through bile acid regulation and further pro-inflammatory responses mediation
- 论文作者：Qiaoling Yang ; Fan Yang ; Junting Gong ; Xiaowen Tang ; Guangyun Wang ; Zhengtao Wang ; Li Yang
- 英文论文作者：Qiaoling Yang ; Fan Yang ; Junting Gong ; Xiaowen Tang ; Guangyun Wang ; Zhengtao Wang ; Li Yang ; The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine(SATCM)Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines ; Institute of Chinese Materia Medica ; Shanghai University of Traditional Chinese Medicine ; Center for Chinese Medical Therapy and Systems Biology ; Shanghai University of Traditional Chinese Medicine
- 年：2016
- 作者机构：The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine(SATCM)Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine;Center for Chinese Medical Therapy and Systems Biology,Shanghai University of Traditional Chinese Medicine;
- 英文论文关键词：sweroside ; ANIT ; cholestasis ; inflammation ; bile acids
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：英文
- 分类号：R285.5
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：19
- 文件大小：2225k
- 原文格式：O
- 会议级别：全国
摘要
Aim:Sweroside,an iridoid glycoside,exerts diverse biological activities.The study aimed to investigate how sweroside attenuates the a-naphthylisothiocyanate(ANIT)-induced cholestatic liver injury in mice.Methods:C57BL mice were treated with sweroside(120 mg/kg,ig) or INT-747(12 mg/kg,ig) for five consecutive days(once daily),respectively.On the 3rd day,4h after sweroside or INT-747 treatment,mice were orally administered a single dose of ANIT in olive oil(75 mg/kg,ig).Serum biochemical markers,histological change,and hepatic bile acids were analyzed.Hepatic pro-inflammatory mediators and bile acid metabolism-related genes were also analyzed.In addition,to explore the role of bile acids in the progress of ANIT-induced liver injury,primary hepatocytes were treated with bile acid milieu,which were composed of the most elevated hepatic individual bile acids after ANIT exposure in vivo study.Results:Sweroside effectively ameliorated ANIT-induced cholestatic liver injury in mice,as evidenced by reduction of serum biochemical markers and attenuation of pathological changes.Furthermore,sweroside dramatically decreased the elevation of hepatic individual bile acids caused by ANIT treatment,such as the P-MCA,CA,and TCA levels.The underlying insights were possibly related to the regulation of mRNA expression of bile acid synthesis,bile acid transports,and pro-inflammatory responses.In addition,overload hepatic bile acids after ANIT exposure may act as an inducer of pro-inflammatory responses.Conclusions:Sweroside effectively attenuated the ANIT-induced cholestatic liver injury in mice by regulating bile acids and restoring their normal levels,as well as repressing pro-inflammatory responses.
Aim:Sweroside,an iridoid glycoside,exerts diverse biological activities.The study aimed to investigate how sweroside attenuates the a-naphthylisothiocyanate(ANIT)-induced cholestatic liver injury in mice.Methods:C57BL mice were treated with sweroside(120 mg/kg,ig) or INT-747(12 mg/kg,ig) for five consecutive days(once daily),respectively.On the 3rd day,4h after sweroside or INT-747 treatment,mice were orally administered a single dose of ANIT in olive oil(75 mg/kg,ig).Serum biochemical markers,histological change,and hepatic bile acids were analyzed.Hepatic pro-inflammatory mediators and bile acid metabolism-related genes were also analyzed.In addition,to explore the role of bile acids in the progress of ANIT-induced liver injury,primary hepatocytes were treated with bile acid milieu,which were composed of the most elevated hepatic individual bile acids after ANIT exposure in vivo study.Results:Sweroside effectively ameliorated ANIT-induced cholestatic liver injury in mice,as evidenced by reduction of serum biochemical markers and attenuation of pathological changes.Furthermore,sweroside dramatically decreased the elevation of hepatic individual bile acids caused by ANIT treatment,such as the P-MCA,CA,and TCA levels.The underlying insights were possibly related to the regulation of mRNA expression of bile acid synthesis,bile acid transports,and pro-inflammatory responses.In addition,overload hepatic bile acids after ANIT exposure may act as an inducer of pro-inflammatory responses.Conclusions:Sweroside effectively attenuated the ANIT-induced cholestatic liver injury in mice by regulating bile acids and restoring their normal levels,as well as repressing pro-inflammatory responses.
Aim:Sweroside,an iridoid glycoside,exerts diverse biological activities.The study aimed to investigate how sweroside attenuates the a-naphthylisothiocyanate(ANIT)-induced cholestatic liver injury in mice.Methods:C57BL mice were treated with sweroside(120 mg/kg,ig) or INT-747(12 mg/kg,ig) for five consecutive days(once daily),respectively.On the 3rd day,4h after sweroside or INT-747 treatment,mice were orally administered a single dose of ANIT in olive oil(75 mg/kg,ig).Serum biochemical markers,histological change,and hepatic bile acids were analyzed.Hepatic pro-inflammatory mediators and bile acid metabolism-related genes were also analyzed.In addition,to explore the role of bile acids in the progress of ANIT-induced liver injury,primary hepatocytes were treated with bile acid milieu,which were composed of the most elevated hepatic individual bile acids after ANIT exposure in vivo study.Results:Sweroside effectively ameliorated ANIT-induced cholestatic liver injury in mice,as evidenced by reduction of serum biochemical markers and attenuation of pathological changes.Furthermore,sweroside dramatically decreased the elevation of hepatic individual bile acids caused by ANIT treatment,such as the P-MCA,CA,and TCA levels.The underlying insights were possibly related to the regulation of mRNA expression of bile acid synthesis,bile acid transports,and pro-inflammatory responses.In addition,overload hepatic bile acids after ANIT exposure may act as an inducer of pro-inflammatory responses.Conclusions:Sweroside effectively attenuated the ANIT-induced cholestatic liver injury in mice by regulating bile acids and restoring their normal levels,as well as repressing pro-inflammatory responses.
引文
1.Wollbright BL,Li F,Xie Y,Farhood A,Fickert P,Trauner M,et al.Lithocholic acid feeding results in direct hepato-toxicity independent of neutrophil function in mice.Toxicol Lett 2014;228(1):56-66.
2.Chatterjee S,Bijsmans IT,van Mil SW,Augustijns P,Annaert P.Toxicity and intracellular accumulation of bile acids in sandwich-cultured rathepatocytes:role of glycine conjugates.Toxicol In Vitro 2014;28(2):218-230.
3.Malhi H,Guicciardi ME,Gores GJ.Hepatocyte death:a clear and present danger.Physiol Rev 2010;90(3):1165-1194.
4.Faubion WA,Guicciardi ME,Miyoshi H,Bronk SF,Roberts PJ,Svingen PA,et al.Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas.J Clin Invest 1999;103(1),137-145.
5.Woolbright BL,Dorko K,Antoine DJ,Clarke JI,Gholami P,Li F,et al.Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis.Toxicol Appl Pharmacol 2015;283(3):168-177.
6.Allen K,Jaeschke H,Copple BL.Bile acids induce inflammatory genes in hepatocytes:a novel mechanism of inflammation during obstructive cholestasis.Am J Pathol 2011;178(1),175-186.
7.O'Brien KM,Allen KM,Rockwell CE,Towery K,Luyendyk JP,et al.IL-I7a synergistically enhances bile acid-induced inflammation during obstructive cholestasis.Am J Pathol 2013;183(5):1498-1507.
8.Paumgartner G Medical treatment of cholestatic liver diseases:from pathobiology to pharmacological targets.World J Gastroenterol 2006;12(28),4445-4451.
9.Ji F,Deng H,Li Z.Eltrombopag for thrombocytopenic patients with hepatitis C virus infection and cirrhosis.Gastroenterology 2014;147(1),253-254.
10.Wang L,Wang J,Shi Y,Zhou X,Wang X,Li Z,et al.Identification of a primary biliary cirrhosis associated protein as lysosome-associated membrane protein-2.J Proteomics 2013;91(1),569-579.
11.Hirschfield GM,Chapman R,Karlsen TH,Lammert F,Lazaridis KN,Mason AL.The genetics of complex cholestatic disorders.Gastroenterology 2013;144(7),1357-1374.
12.Yang F,Xu Y,Xiong A,He Y,Yang L,Wang Z.Evaluation of the protctive effect of Rhei Radix et Rhizoma against a-naphthylisothiocyanate induced liver injury based on metabolic profile of bile acids.J Ethnopharmacol 2012;18;144(3):599-560.
13.Ding L,Zhang B,Zhan C,Yang L,Wang Z.Danning tablets attenuates a-naphthylisothiocyanate induced cholestasis by modulating the expression of transporters and metabolic enzymes.BMC Complement Altera Med 2014;14(1):249.
14.Yan JY,Ai G,Zhang XJ,Xu HJ,Huang ZM.Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot(L.)Medic against o-naphthylisothio cyanate-induced cholestatic liver injury in rats.J Ethnopharmacol 2015;172:202-213
15.Erlinger S.What is cholestasis in 1985?J Hepatol 1985;1(6):687-693.
16.Kodali P,Wu P,Lahiji PA,Brown EJ,Maher JJ.ANIT toxicity toward mouse hepatocytes in vivo is mediated primarily by neutrophils via CD18.Am J Physiol Gastrointest Liver Physiol 2006;291(2):G355-G363.
17.Guo C,He L,Yao D,A J,Cao B,Ren J,et al.Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocyte.Toxicol Lett 2014;224(1):93-100.
18.Choi Y,Yi NJ,Ko JS,Ko JM,Jin US,Kim HS,et al.Living donor liver transplantation for an infent with osteogenesis imperfecta and intrahepatic cholestasis:report of a case.J Korean Med Sci 2014;29(3):441-444.
19.Hirschfield GM,Heathcote EJ,Gershwin ME.Pathogenesis of cholestatic liver disease and therapeutic approaches.Gastroenterology 2010;139(5):1481-1496.
20.Beuers U,Trauner M,Jansen P,Poupon R.New paradigms in the treatment of hepatic cholestasis:from UDCA to FXR,PXR and beyond.J Hepatol 2015;62(1):S25-S37.
21.Fickert P,Pollheimer MJ,Silbert D,Moustafe T,Halilbile acidsic E,Krones E,et al.Differential effects of nor UDCA and UDCA in obstructive cholestasis in mice.J Hepatol 2013;58(6):1201-1208.
22.Fiorucci S,Cipriani S,Mencarelli A,Baldelli F,.Bifulco Q Zampella A.Farnesoid X receptor agonist for the treatment of liver and metabolic disorders:focus on 6-ethyl-CDCA.Mini Rev Med Chem 2011;11(9):753-762.
23.Tan RX,Wolfender JL,Ma WG,Zhang LX,Hostettmann K.Secoiridoids and anti-fungal aromatic acids from Gentiana algida.Phytochemistry 1996;41(1):111-116.
24.Hase K,Li JX,Basnet P,Xiong Q,Takamura SC,Namba T,et al.Hepatoprotec-tive principles of Swertia japonica Makino on D-galactosamine/lipopolysaccharide-induced liver injury in mice.Chem Pharm Bull 1997;45(11):1823-1827.
25.Mahendran G,T hamotharan G,Sengottuvelu S,Narmtha Bai V.Anti-diabetic activity of Swertia corymbosa(Griseb.)Wight ex C.B.Clarke aerial parts extract in streptozotocin induced diabetic rats.J Ethnopharmacol 2014;151(3):1175-1183.
26.Sun H,Li L,Zhang A,Zhang N,Lv H,Sun W,et al.Protective effects of sweroside on human MG-63 cells and rat osteoblasts.Fitoterapia2013;84(1):174-179.
27.Jeong YT,Jeong SC,Hwang JS,Kim JH.Modulation effects of sweroside isolated from the Lonicera japonica on melanin synthesis.Chem Biol Interact 2015;238(1):33-39.
28.He YM,Zhu S,Ge YW,Kazuma K,Zou K,Cai SQ,et al.The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae Radix:the root and rhizome of Gentiana scabra.J Nat Med 2015;69(3):303-312.
29.Chen F,Ananthanarayanan M,Emre S,Neimark E,Bull LN,Knisely AS,et al.Progressive familial intrahepatic cholestasis,type 1,is associated with decreased farnesoid X receptor activity.Gastroenterology 2004;126(3):756-764.
30.Strautnieks SS,Bull LN,Knisely AS,Kocoshis SA,Dahl N,Arnell H,et al.A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.Nat Genet 1998;20(3):233-238.
31.van Mil SWC,van der Woerd WL,van der Brugge G,Sturm E,Jansen PLM,Bull LN,et al.Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11.Gastroenterology 2004;127(2):379-384.
32.Cui YJ,Aleksunes LM,Tanaka Y,Goedken MJ,Klaassen CD.Compensatory induction of liver efflux transporters in response to ANIT-induced liver injury is impaired in FXR-null mice.Toxicol Sci 2009;110(1):47-60.
33.Thatch KA,Schwartz MZ,Yoo EY,Mendelson KG,Duke DS.Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model:a potential approach to the management and treatment of cholestatic liver disease.J Pediatr Surg 2008;43(12):2169-2173.
34.Wang T,Zhou ZX,Sun LX,Li X,Xu ZM,Chen M,et al.Resveratrol effectively attenuates a-naphthyl-isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms.Acta Pharmacol Sin 2014;35(12):1527-1536.
35.Liu Y,Binz J,Numerick MJ,Dennis S,Luo G,Desai B,et al.Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intrahepatic and extrahepatic cholestasis.J Clin Invest 2003;112:1878-1887.
36.Guo C,He L,Yao D,A J,Cao B,Ren J,et al.Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocytes.Toxicol Lett 2014;224(1):93-100.
37.Keppler D.Multidrug resistance proteins(MRPs,ABCCs):importance for pathophysiology and drug therapy.Handb Exp Pharmacol 2011;201(1):299-323.
38.Dietrich CQ Ottenhoff R,de Waart DR,Oude Elferink RPJ.Role of Mrp2 and GSH in intrahepatic cycling of toxins.Toxicology 2001;167(1),73-81.
39.Boyer JL,Trauner M,Mennone A,Soroka CJ,Cai SY,Moustafa T,et al.Up-regulation of a basolateral FXR-dependent bile acid efflux transporter OST alpha-OST beta in cholestasis in humans and rodents.Am J Physiol Gastrointest Liver Physiol 2006;290(6):G1124-G1130.
40.Zollner G,Fickert P,Zenz R,Fuchsbichler A,Stumptner C,Kenner L,et al.Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.Hepatology 2001;33(3):633-646.
41.Zhang Y,Csanaky IL,Lehman-McKeeman LD,Klaassen CD.Loss of organic anion transporting polypeptide lal increases deoxycholic acid absorption in mice by increasing intestinal permeability.Toxicol Sci 2011;124:251-260.
42.Denson LA,Bohan A,Held MA,Boyer JL.Organ-specific alterations in RAR alpha:RXR alpha abundance regulate rat Mrp2(Abcc2)expression in obstructive cholestasis.Gastroenterology 2002;123(2):599-607.
43.Jahan A,Chiang JY.Cytokine regulation of human sterol 12alpha-hydroxylase(CYP8B1)gene.Am J Physiol Gastrointest Liver Physiol 2005;288(4):G685-G695.
44.Li T,Jahan A,Chiang JY.Bile acids and cytokines inhibit the human cholesterol 7 alpha-hydroxylase gene via the JNK/c-jun pathway in human liver cells.Hepatology 2006;43(6):1202-1210.
45.Geier A,Dietrich CQ Trauner M,Gartung C.Extrahepatic cholestasis down-regulates Oatpl by TNF-alpha signaling without affecting Oatp2 and Oatp4 expression and sodium-independent bile salt uptake in rat liver.Liver Int2007;27(8):1056-1065.
46.Yang L,Xiong A,He Y,Wang Z,Wang C,et al.Bile acids metabonomics study on the CC14-and a-Naphthylisothiocyanate-Induced animal models:Quantitative analysis of 22 bile acids by Ultraperformance Lipid Chromatography-Mass Spectrometry.Chem Res Toxicol.2008;21:2280-2288.
2.Chatterjee S,Bijsmans IT,van Mil SW,Augustijns P,Annaert P.Toxicity and intracellular accumulation of bile acids in sandwich-cultured rathepatocytes:role of glycine conjugates.Toxicol In Vitro 2014;28(2):218-230.
3.Malhi H,Guicciardi ME,Gores GJ.Hepatocyte death:a clear and present danger.Physiol Rev 2010;90(3):1165-1194.
4.Faubion WA,Guicciardi ME,Miyoshi H,Bronk SF,Roberts PJ,Svingen PA,et al.Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas.J Clin Invest 1999;103(1),137-145.
5.Woolbright BL,Dorko K,Antoine DJ,Clarke JI,Gholami P,Li F,et al.Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis.Toxicol Appl Pharmacol 2015;283(3):168-177.
6.Allen K,Jaeschke H,Copple BL.Bile acids induce inflammatory genes in hepatocytes:a novel mechanism of inflammation during obstructive cholestasis.Am J Pathol 2011;178(1),175-186.
7.O'Brien KM,Allen KM,Rockwell CE,Towery K,Luyendyk JP,et al.IL-I7a synergistically enhances bile acid-induced inflammation during obstructive cholestasis.Am J Pathol 2013;183(5):1498-1507.
8.Paumgartner G Medical treatment of cholestatic liver diseases:from pathobiology to pharmacological targets.World J Gastroenterol 2006;12(28),4445-4451.
9.Ji F,Deng H,Li Z.Eltrombopag for thrombocytopenic patients with hepatitis C virus infection and cirrhosis.Gastroenterology 2014;147(1),253-254.
10.Wang L,Wang J,Shi Y,Zhou X,Wang X,Li Z,et al.Identification of a primary biliary cirrhosis associated protein as lysosome-associated membrane protein-2.J Proteomics 2013;91(1),569-579.
11.Hirschfield GM,Chapman R,Karlsen TH,Lammert F,Lazaridis KN,Mason AL.The genetics of complex cholestatic disorders.Gastroenterology 2013;144(7),1357-1374.
12.Yang F,Xu Y,Xiong A,He Y,Yang L,Wang Z.Evaluation of the protctive effect of Rhei Radix et Rhizoma against a-naphthylisothiocyanate induced liver injury based on metabolic profile of bile acids.J Ethnopharmacol 2012;18;144(3):599-560.
13.Ding L,Zhang B,Zhan C,Yang L,Wang Z.Danning tablets attenuates a-naphthylisothiocyanate induced cholestasis by modulating the expression of transporters and metabolic enzymes.BMC Complement Altera Med 2014;14(1):249.
14.Yan JY,Ai G,Zhang XJ,Xu HJ,Huang ZM.Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot(L.)Medic against o-naphthylisothio cyanate-induced cholestatic liver injury in rats.J Ethnopharmacol 2015;172:202-213
15.Erlinger S.What is cholestasis in 1985?J Hepatol 1985;1(6):687-693.
16.Kodali P,Wu P,Lahiji PA,Brown EJ,Maher JJ.ANIT toxicity toward mouse hepatocytes in vivo is mediated primarily by neutrophils via CD18.Am J Physiol Gastrointest Liver Physiol 2006;291(2):G355-G363.
17.Guo C,He L,Yao D,A J,Cao B,Ren J,et al.Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocyte.Toxicol Lett 2014;224(1):93-100.
18.Choi Y,Yi NJ,Ko JS,Ko JM,Jin US,Kim HS,et al.Living donor liver transplantation for an infent with osteogenesis imperfecta and intrahepatic cholestasis:report of a case.J Korean Med Sci 2014;29(3):441-444.
19.Hirschfield GM,Heathcote EJ,Gershwin ME.Pathogenesis of cholestatic liver disease and therapeutic approaches.Gastroenterology 2010;139(5):1481-1496.
20.Beuers U,Trauner M,Jansen P,Poupon R.New paradigms in the treatment of hepatic cholestasis:from UDCA to FXR,PXR and beyond.J Hepatol 2015;62(1):S25-S37.
21.Fickert P,Pollheimer MJ,Silbert D,Moustafe T,Halilbile acidsic E,Krones E,et al.Differential effects of nor UDCA and UDCA in obstructive cholestasis in mice.J Hepatol 2013;58(6):1201-1208.
22.Fiorucci S,Cipriani S,Mencarelli A,Baldelli F,.Bifulco Q Zampella A.Farnesoid X receptor agonist for the treatment of liver and metabolic disorders:focus on 6-ethyl-CDCA.Mini Rev Med Chem 2011;11(9):753-762.
23.Tan RX,Wolfender JL,Ma WG,Zhang LX,Hostettmann K.Secoiridoids and anti-fungal aromatic acids from Gentiana algida.Phytochemistry 1996;41(1):111-116.
24.Hase K,Li JX,Basnet P,Xiong Q,Takamura SC,Namba T,et al.Hepatoprotec-tive principles of Swertia japonica Makino on D-galactosamine/lipopolysaccharide-induced liver injury in mice.Chem Pharm Bull 1997;45(11):1823-1827.
25.Mahendran G,T hamotharan G,Sengottuvelu S,Narmtha Bai V.Anti-diabetic activity of Swertia corymbosa(Griseb.)Wight ex C.B.Clarke aerial parts extract in streptozotocin induced diabetic rats.J Ethnopharmacol 2014;151(3):1175-1183.
26.Sun H,Li L,Zhang A,Zhang N,Lv H,Sun W,et al.Protective effects of sweroside on human MG-63 cells and rat osteoblasts.Fitoterapia2013;84(1):174-179.
27.Jeong YT,Jeong SC,Hwang JS,Kim JH.Modulation effects of sweroside isolated from the Lonicera japonica on melanin synthesis.Chem Biol Interact 2015;238(1):33-39.
28.He YM,Zhu S,Ge YW,Kazuma K,Zou K,Cai SQ,et al.The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae Radix:the root and rhizome of Gentiana scabra.J Nat Med 2015;69(3):303-312.
29.Chen F,Ananthanarayanan M,Emre S,Neimark E,Bull LN,Knisely AS,et al.Progressive familial intrahepatic cholestasis,type 1,is associated with decreased farnesoid X receptor activity.Gastroenterology 2004;126(3):756-764.
30.Strautnieks SS,Bull LN,Knisely AS,Kocoshis SA,Dahl N,Arnell H,et al.A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.Nat Genet 1998;20(3):233-238.
31.van Mil SWC,van der Woerd WL,van der Brugge G,Sturm E,Jansen PLM,Bull LN,et al.Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11.Gastroenterology 2004;127(2):379-384.
32.Cui YJ,Aleksunes LM,Tanaka Y,Goedken MJ,Klaassen CD.Compensatory induction of liver efflux transporters in response to ANIT-induced liver injury is impaired in FXR-null mice.Toxicol Sci 2009;110(1):47-60.
33.Thatch KA,Schwartz MZ,Yoo EY,Mendelson KG,Duke DS.Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model:a potential approach to the management and treatment of cholestatic liver disease.J Pediatr Surg 2008;43(12):2169-2173.
34.Wang T,Zhou ZX,Sun LX,Li X,Xu ZM,Chen M,et al.Resveratrol effectively attenuates a-naphthyl-isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms.Acta Pharmacol Sin 2014;35(12):1527-1536.
35.Liu Y,Binz J,Numerick MJ,Dennis S,Luo G,Desai B,et al.Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intrahepatic and extrahepatic cholestasis.J Clin Invest 2003;112:1878-1887.
36.Guo C,He L,Yao D,A J,Cao B,Ren J,et al.Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocytes.Toxicol Lett 2014;224(1):93-100.
37.Keppler D.Multidrug resistance proteins(MRPs,ABCCs):importance for pathophysiology and drug therapy.Handb Exp Pharmacol 2011;201(1):299-323.
38.Dietrich CQ Ottenhoff R,de Waart DR,Oude Elferink RPJ.Role of Mrp2 and GSH in intrahepatic cycling of toxins.Toxicology 2001;167(1),73-81.
39.Boyer JL,Trauner M,Mennone A,Soroka CJ,Cai SY,Moustafa T,et al.Up-regulation of a basolateral FXR-dependent bile acid efflux transporter OST alpha-OST beta in cholestasis in humans and rodents.Am J Physiol Gastrointest Liver Physiol 2006;290(6):G1124-G1130.
40.Zollner G,Fickert P,Zenz R,Fuchsbichler A,Stumptner C,Kenner L,et al.Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.Hepatology 2001;33(3):633-646.
41.Zhang Y,Csanaky IL,Lehman-McKeeman LD,Klaassen CD.Loss of organic anion transporting polypeptide lal increases deoxycholic acid absorption in mice by increasing intestinal permeability.Toxicol Sci 2011;124:251-260.
42.Denson LA,Bohan A,Held MA,Boyer JL.Organ-specific alterations in RAR alpha:RXR alpha abundance regulate rat Mrp2(Abcc2)expression in obstructive cholestasis.Gastroenterology 2002;123(2):599-607.
43.Jahan A,Chiang JY.Cytokine regulation of human sterol 12alpha-hydroxylase(CYP8B1)gene.Am J Physiol Gastrointest Liver Physiol 2005;288(4):G685-G695.
44.Li T,Jahan A,Chiang JY.Bile acids and cytokines inhibit the human cholesterol 7 alpha-hydroxylase gene via the JNK/c-jun pathway in human liver cells.Hepatology 2006;43(6):1202-1210.
45.Geier A,Dietrich CQ Trauner M,Gartung C.Extrahepatic cholestasis down-regulates Oatpl by TNF-alpha signaling without affecting Oatp2 and Oatp4 expression and sodium-independent bile salt uptake in rat liver.Liver Int2007;27(8):1056-1065.
46.Yang L,Xiong A,He Y,Wang Z,Wang C,et al.Bile acids metabonomics study on the CC14-and a-Naphthylisothiocyanate-Induced animal models:Quantitative analysis of 22 bile acids by Ultraperformance Lipid Chromatography-Mass Spectrometry.Chem Res Toxicol.2008;21:2280-2288.