胆汁淤积动物模型的构建及应用前景

杜丽娜; 杨燕

doi:10.3969/j.issn.1001-5256.2019.02.046

胆汁淤积动物模型的构建及应用前景

DOI: 10.3969/j.issn.1001-5256.2019.02.046

杜丽娜,
杨燕

国家儿童医学中心/首都医科大学附属北京儿童医院中医科

基金项目:

国家自然科学基金面上项目(81473725)；

详细信息

中图分类号: R575;R-332
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- 被引次数: 0
出版历程
- 收稿日期: 2018-10-08
- 出版日期: 2019-02-20

Establishment and application of animal models of cholestasis

Du LiNa,
Yang Yan

Department of Traditional Chinese Medicine, Beijing Children's Hospital, Capital Medical University/National Center for Children's Health

Research funding:

摘要

摘要: 胆汁淤积性肝病是1岁以内儿童常见病之一,其病因复杂,预后不一,为进一步深入研究其发病机制及治疗策略,研究者建立了多种不同的胆汁淤积动物模型。如通过手术或外界物理化学损伤建立梗阻型胆汁淤积模型;通过化学药品或内毒素诱导建立肝内胆汁淤积模型,包括α-萘异硫氰酸酯、脂多糖、3,5-二乙氧基羰基-1,4-二氢三甲基吡啶、雌激素、氯丙嗪、利福平、石胆酸等;或通过肠道损伤与肠外营养相结合建立肠外营养相关胆汁淤积模型。各类模型体现了不同的病因和发展过程。现对医学研究中较常用的胆汁淤积动物模型特点及机理、适应证作一综述。
- 胆汁淤积 /
- 模型,动物 /
- 综述
Abstract: Cholestatic liver disease is one of the common diseases in children aged < 1 year and has a complex etiology and different outcomes. Various animal models have been established to further investigate the pathogenesis of cholestatic liver disease and related treatment strategies. A model of obstructive cholestasis is established by surgery or external physical and chemical damage; a model of intrahepatic cholestasis is induced by chemicals or endotoxins, including α-naphthyl isothiocyanate, lipopolysaccharide, 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine, estrogen, chlorpromazine, rifampicin, and lithocholic acid; a model of parenteral nutrition-associated cholestasis is established by a combination of intestinal damage and parenteral nutrition. These models reflect different causes and development processes.This article reviews the characteristics, mechanisms, and indications of animal models of cholestasis commonly used in medical research.
- cholestasis /
- models, animal /
- review

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参考文献(29)

[1]Chinese Society of Hepatology, Chinese Medical Association;Chinese Society of Gastroenterology, Chinese Medical Association;Chinese Society of Infectious Diseases, Chinese Medical Association.Consensus on the diagnosis and treatment of cholestasis liver diseases (2015) [J].J Clin Hepatol, 2015, 31 (12) :1989-1999. (in Chinese) 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会.胆汁淤积性肝病诊断和治疗共识 (2015) [J].临床肝胆病杂志, 2015, 31 (12) :1989-1999.

[2]KIM TW, LEE HK, SONG IB, et al.Platycodin D attenuates bile duct ligation-induced hepatic injury and fibrosis in mice[J].Food Chem Toxicol, 2013, 51:364-369.

[3]HEINRICH S, GEORGIEV P, WEBER A, et al.Partial bile duct ligation in mice:A novel model of acute cholestasis[J].Surgery, 2011, 149 (3) :445-451.

[4]YOKOTA S, ONO Y, NAKAO T, et al.Partial bile duct ligation in the mouse:A controlled model of localized obstructive cholestasis[J].J Vis Exp, 2018.[Epub ahead of print]

[5]XUAN J, TIAN YZ, CAO P, et al.Improvement in the rat model of liver fibrosis induced by bile duct ligation[J].Chin JComp Med, 2014, 24 (4) :57-61. (in Chinese) 宣佶, 田耀洲, 曹鹏, 等.胆汁淤积性肝硬化大鼠模型的改良[J].中国比较医学杂志, 2014, 24 (4) :57-61.

[6]LUO WW, YU SP.Research advances in animal models of obstructive jaundice[J].J Clin Hepatol, 2017, 33 (9) :1820-1823. (in Chinese) 骆伟伟, 余水平.梗阻性黄疸动物模型的研究进展[J].临床肝胆病杂志, 2017, 33 (9) :1820-1823.

[7]CHEN FF, LU Z, FU XJ, et al.Establishment of a new rat model of reversible obstructive jaundice[J].Chin J Exp Surg, 2018, 35 (9) :1767-1770. (in Chinese) 陈芳芳, 鲁正, 付晓君, 等.一种新型可复性梗阻性黄疸大鼠模型的建立[J].中华实验外科学杂志, 2018, 35 (9) :1767-1770.

[8]DIETRICH CG, OTTENHOFF R, de WAART DR, et al.Role of MRP2 and GSH in intrahepatic cycling of toxins[J].Toxicology, 2001, 167 (1) :73-81.

[9]LI H, LI YM, LU L.Mechanism ofα-naphthyl isothiocyanate inducing cholestatic hepatitis:A preliminary study[J].J Clin Hepatol, 2016, 32 (5) :933-937. (in Chinese) 李华, 黎一鸣, 卢乐.α-异硫氰酸萘酯致胆汁淤积性肝炎的发生机制初探[J].临床肝胆病杂志, 2016, 32 (5) :933-937.

[10]YANG T, MEI H, XU D, et al.Early indications of ANIT-induced cholestatic liver injury:Alteration of hepatocyte polarization and bile acid homeostasis[J].Food Chem Toxicol, 2017, 110:1-12.

[11]SUI JL, SUN FX, LI P, et al.Pathological and biochemical effects of Yinchenhao Decoction on acute intrahepatic cholestasis rats[J].J Clin Exp Med, 2018, 17 (19) :2033-2036. (in Chinese) 隋京利, 孙凤霞, 李攀, 等.茵陈蒿汤对急性肝内胆汁淤积模型大鼠生化指标及肝脏病理变化影响研究[J].临床和实验医学杂志, 2018, 17 (19) :2033-2036.

[12]OU QQ, QIAN XH, HUANG XQ, et al.The biochemical and pathological changes of ANIT induced sub-acute cholestasis in infantile rats[J].Chin J Gastroenterol Hepatol, 2015, 24 (4) :463-465. (in Chinese) 欧巧群, 钱新华, 黄笑群, 等.ANIT诱导大鼠亚急性肝内胆汁淤积的生化和病理变化[J].胃肠病学和肝病学杂志, 2015, 24 (4) :463-465.

[13]YAN HF, XU BX, LI XO, et al.Effects of lipopolysaccharide on proliferation, secretion and ultrastructure of Kupffer cells in liver[J].Med&Pharm J Chin PLA, 2017, 29 (10) :1-4. (in Chinese) 闫洪锋, 徐冰心, 李晓鸥, 等.脂多糖对肝脏Kupffer细胞增殖和分泌功能及超微结构的影响[J].解放军医药杂志, 2017, 29 (10) :1-4.

[14]YANG P, ZHOU W, LI C, et al.Kupffer-cell-expressed transmembrane TNF-αis a major contributor to lipopolysaccharide and D-galactosamine-induced liver injury[J].Cell Tissue Res, 2016, 363 (2) :371-383.

[15]XIONG X, REN Y, CUI Y, et al.Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation[J].Biomed Pharmacother, 2017, 96:1292-1298.

[16]CHEN J, ZHAO KN, LIU GB.Estrogen-induced cholestasis:Pathogenesis and therapeuticimplications[J].Hepatogastroenterology, 2013, 60 (126) :1289-1296.

[17]MISZCZUK GS, BAROSSO IR, LAROCCA MC, et al.Mechanisms of canalicular transporter endocytosis in the cholestatic rat liver[J].Biochim Biophys Acta Mol Basis Dis, 2018, 1864 (4 Pt A) :1072-1085.

[18]DI GUIDA F, PIROZZI C, MAGLIOCCA S, et al.Galactosylated pro-drug of ursodeoxycholic acid:Design, synthesis, characterization, and pharmacological effects in a rat model of estrogen-induced cholestasis[J].Mol Pharm, 2018, 15 (1) :21-30.

[19]ANTHRIEU S, BACHOUR-EL AZZI P, DUMONT J, et al.Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells[J].Hepatology, 2013, 57 (4) :1518-1529.

[20]YANG Q, YANG F, TANG X, et al.Chlorpromazine-induced perturbations of bile acids and free fatty acids in cholestatic liver injury prevented by the Chinese herbal compound YinChen-Hao-Tang[J].BMC Complement Altern Med, 2015, 15:122.

[21]CHEN X, ZHANG C, WANG H, et al.Altered integrity and decreased expression of hepatocyte tight junctions in rifampicin-induced cholestasis in mice[J].Toxicol Appl Pharmacol, 2009, 240 (1) :26-36.

[22]CAO YH, CHEN X, ZHANG C, et al.Change of expression and localization of canalicular Bsep and Mrp2 in rifampicininduced cholestasis in mice[J].Chin Pharmacol Bull, 2010, 26 (12) :1581-1586. (in Chinese) 曹云海, 陈熙, 张程, 等.利福平对小鼠肝细胞胆汁酸转运体Bsep和Mrp2表达与定位的影响[J].中国药理学通报, 2010, 26 (12) :1581-1586.

[23]CAI Y, REN XF, WANG W, et al.Adaptation phenomenon of cholestatic hepatic injury induced by rifampicin in rats[J].Chin J Gastroenterol, 2013, 18 (3) :134-138. (in Chinese) 蔡轶, 任晓非, 王巍, 等.利福平致大鼠胆汁淤积性肝损伤适应性现象的研究[J].胃肠病学, 2013, 18 (3) :134-138.

[24]YANG R, ZHAO Q, HU DD, et al.Metabolomic analysis of cholestatic liver damage in mice[J].Food Chem Toxicol, 2018, 120:253-260.

[25]WOOLBRIGHT BL, LI F, XIE Y, et al.Lithocholic acid feeding results in direct hepato-toxicity independent of neutrophil function in mice[J].Toxicol Lett, 2014, 228 (1) :56-66.

[26]ZHANG H, BIAN ZL, WANG QX, et al.Establishment and evaluation of cholestatic mice model[J].Chin Hepatol, 2015, 20 (3) :218-222. (in Chinese) 张慧, 卞兆连, 王绮夏, 等.胆汁淤积小鼠模型的探讨[J].肝脏, 2015, 20 (3) :218-222.

[27]MARIOTTI V, STRAZZABOSCO M, FABRIS L, et al.Animal models of biliary injury and altered bile acid metabolism[J].Biochim Biophys Acta Mol Basis Dis, 2018, 1864 (4 Pt B) :1254-1261.

[28]CAI RH, YANG CY, XIU WL, et al.Effects of MCT/LCT and LCT fatty acid on parenteral nutrition-associated cholestasis in premature infants[J].Chin J Clin Pharmacol Ther, 2017, 22 (10) :1167-1171. (in Chinese) 蔡瑞宏, 杨长仪, 修文龙, 等.中/长链脂肪乳及长链脂肪乳对早产儿静脉营养性胆汁淤积的影响[J].中国临床药理学与治疗学, 2017, 22 (10) :1167-1171.

[29]EL KASMI KC, VUE PM, ANDERSON AL, et al.Macrophage-derived IL-1β/NF-κB signaling mediates parenteral nutrition-associated cholestasis[J].Nat Commun, 2018, 9 (1) :1393.

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