原发性胆汁性胆管炎的动物模型

郝娟; 刘成海

doi:10.3969/j.issn.1001-5256.2017.11.013

原发性胆汁性胆管炎的动物模型

DOI: 10.3969/j.issn.1001-5256.2017.11.013

郝娟,
刘成海

1. 上海中医药大学附属曙光医院肝病研究所
2. 上海市中医临床重点实验室
3. 上海高校中医内科学E-研究院

详细信息

中图分类号: R-332;R575.22
计量
- 文章访问数: 2282
- HTML全文浏览量: 36
- PDF下载量: 597
- 被引次数: 0
出版历程
- 收稿日期: 2017-09-01
- 出版日期: 2017-11-20

A study on animal models of primary biliary cholangitis

Institute of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

摘要

摘要: 理想的原发性胆汁性胆管炎(PBC)动物模型对于研究疾病的病理生理机制与药物研发等均有重要意义。近年来可反映血清抗线粒体抗体阳性与胆管免疫病理损伤等PBC特点的动物模型取得了较大进展。目前PBC动物模型的制备方式多样,包括化学或生物染毒诱导,以及基因敲除后自发形成。但上述模型尚无法完全模拟人类PBC,其血清学、免疫学、组织病理等方面也各有特点,提示PBC基因特异与环境改变的病理机制的复杂性,对认识免疫耐受性被打破和胆管上皮细胞受到特异性攻击等PBC早期事件的机制具有重要意义。
- 胆管炎,胆汁性 /
- 模型,动物
Abstract: An ideal animal model of primary biliary cholangitis (PBC) plays an important role in the research on physiopathological mechanism and drug research and development.In recent years, great achievements have been made in animal models which can reflect the features of PBC, such as positive serum anti-mitochondrial antibody and immunopathological injury of the bile duct.There are various methods for the preparation of animal models of PBC at present, including chemical or biological exposure and gene knockout.However, these models cannot completely simulate PBC in humans, since they have different serological, immunological, and histopathological features.This suggests the complexity of pathological mechanisms of PBC, including gene specificity and environmental changes and helps us to understand the pathogenesis of events in the early stage of PBC, such as the break of immune tolerance and specific attack of biliary epithelial cells.
- cholangitis, biliary /
- models, animal

HTML全文

参考文献(37)

[1]WEBB GJ, HIRSCHFIELD GM.Primary biliary cholangitis in2016:high-definition PBC:biology, models and therapeutic advances[J].Nat Rev Gastroenterol Hepatol, 2017, 14 (2) :76-78.

[2]CHEN CW, CHENG J, DOU XG, et al.Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis) (2015) [J].J Clin Hepatol, 2015, 31 (12) :1980-1988. (in Chinese) 陈成伟, 成军, 窦晓光, 等.原发性胆汁性肝硬化 (又名原发性胆汁性胆管炎) 诊断和治疗共识 (2015) [J].临床肝胆病杂志, 2015, 31 (12) :1980-1988.

[3]GORELIK L, FLAVELL RA.Abrogation of TGFbeta signaling in Tcells leads to spontaneous T cell differentiation and autoimmune disease[J].Immunity, 2000, 12 (2) :171-181.

[4]OERTELT S, LIAN ZX, CHENG CM, et al.Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptorⅡdominant-negative mice[J].J Immunol, 2006, 177 (3) :1655-1660.

[5]LI MO, WAN YY, SANJABI S, et al.Transforming growth factor-beta regulation of immune responses[J].Annu Rev Immunol, 2006, 24:99-146.

[6]ANDO Y, YANG GX, KENNY TP, et al.Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-beta receptor typeⅡmouse[J].J Autoimmun, 2013, 41:111-119.

[7]CHUANG YH, LIAN ZX, YANG GX, et al.Natural killer T cells exacerbate liver injury in a transforming growth factor beta receptorⅡdominant-negative mouse model of primary biliary cirrhosis[J].Hepatology, 2008, 47 (2) :571-580.

[8]KAWATA K, YANG GX, ANDO Y, et al.Clonality, activated antigen-specific CD8 (+) T cells, and development of autoimmune cholangitis in dn TGFbetaRⅡmice[J].Hepatology, 2013, 58 (3) :1094-1104.

[9]KOARADA S, WU Y, FERTIG N, et al.Genetic control of autoimmunity:protection from diabetes, but spontaneous autoimmune biliary disease in a nonobese diabetic congenic strain[J].J Immunol, 2004, 173 (4) :2315-2323.

[10]IRIE J, WU Y, WICKER LS, et al.NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis[J].The J Exp Med, 2006, 203 (5) :1209-1219.

[11]WANG J, YANG GX, TSUNEYAMA K, et al.Animal models of primary biliary cirrhosis[J].Semin Liver Dis, 2014, 34 (3) :285-296.

[12]TERASAKI S, NAKANUMA Y, YAMAZAKI M, et al.Eosinophilic infiltration of the liver in primary biliary cirrhosis:a morphological study[J].Hepatology, 1993, 17 (2) :206-212.

[13]ROMERO MF, CHEN AP, PARKER MD, et al.The SLC4 family of bicarbonate (HCO (3) (-) ) transporters[J].Mol Aspects Med, 2013, 34 (2-3) :159-182.

[14]LIU Y, YANG J, CHEN LM.Structure and function of SLC4 family[Formula:see text]transporters[J].Front Physiol, 2015, 6:355.

[15]ALPER SL.Molecular physiology and genetics of Na+-independent SLC4 anion exchangers[J].J Exp Biol, 2009, 212 (Pt 11) :1672-1683.

[16]ALPER SL.Molecular physiology of SLC4 anion exchangers[J].Exp Physiol, 2006, 91 (1) :153-161.

[17]SALAS JT, BANALES JM, SARVIDE S, et al.Ae2a, b-deficient mice develop antimitochondrial antibodies and other features resembling[J].Gastroenterology, 2008, 134 (5) :1482-1493.

[18]PRIETO J, GARCIA N, MARTI-CLIMENT JM, et al.Assessment of biliary bicarbonate secretion in humans by positron emission tomography[J].Gastroenterology, 1999, 117 (1) :167-172.

[19]MEDINA JF, MARTINEZ A, VAZQUEZ JJ, et al.Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis[J].Hepatology, 1997, 25 (1) :12-17.

[20]MEDINA JF.Role of the anion exchanger 2 in the pathogenesis and treatment of primary biliary cirrhosis[J].Dig Dis, 2011, 29 (1) :103-112.

[21]BANALES JM, SAEZ E, URIZ M, et al.Up-regulation of microRNA 506 leads to decreased Cl-/HCO3-anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis[J].Hepatology, 2012, 56 (2) :687-697.

[22]CORPECHOT C, CARRAT F, BAHR A, et al.The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis[J].Gastroenterology, 2005, 128 (2) :297-303.

[23]PRIETO J, QIAN C, GARCIA N, et al.Abnormal expression of anion exchanger genes in primary biliary cirrhosis[J].Gastroenterology, 1993, 105 (2) :572-578.

[24]CONCEPCION AR, SALAS JT, SARVIDE S, et al.Anion exchanger 2 is critical for CD8 (+) T cells to maintain p Hi homeostasis and modulate immune responses[J].Eur J Immunol, 2014, 44 (5) :1341-1351.

[25]MARDONES P, MEDINA JF, ELFERINK RP.Activation of cyclic AMP signaling in Ae2-deficient mouse fibroblasts[J].J Biol Chem, 2008, 283 (18) :12146-12153.

[26]HODGE DL, BERTHET C, COPPOLA V, et al.IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice[J].J Autoimmun, 2014, 53:33-45.

[27]BAE HR, LEUNG PS, TSUNEYAMA K, et al.Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance[J].Hepatology, 2016, 64 (4) :1189-1201.

[28]WAKABAYASHI K, LIAN ZX, LEUNG PS, et al.Loss of tolerance in C57BL/6 mice to the autoantigen E2 subunit of pyruvate dehydrogenase by a xenobiotic with ensuing biliary ductular disease[J].Hepatology, 2008, 48 (2) :531-540.

[29]OKADA C, AKBAR SM, HORIIKE N, et al.Early development of primary biliary cirrhosis in female C57BL/6 mice because of poly I∶Cadministration[J].Liver Int, 2005, 25 (3) :595-603.

[30]AMBROSINI YM, YANG GX, ZHANG W, et al.The multi-hit hypothesis of primary biliary cirrhosis:polyinosinic-polycytidylic acid (poly I∶C) and murine autoimmune cholangitis[J].Clin Exp Immunol, 2011, 166 (1) :110-120.

[31]BOGDANOS DP, BAUM H, GRASSO A, et al.Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis[J].J Hepatol, 2004, 40 (1) :31-39.

[32]WANG JJ, YANG GX, ZHANG WC, et al.Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrial antibodies in non-obese diabetic (NOD) .B6 (Idd10/Idd18) mice[J].Clin Exp Immunol, 2014, 175 (2) :192-201.

[33]JIANG T, HAN Z, CHEN S, et al.Resistance to activation-induced cell death and elevated FLIPL expression of CD4+T cells in a polyⅠ:C-induced primary biliary cirrhosis mouse model[J].Clin Exp Med, 2009, 9 (4) :269-276.

[34]BOGDANOS DP, KOUTSOUMPAS A, BAUM H, et al.Borrelia Burgdorferi:a new self-mimicking trigger in primary biliary cirrhosis[J].Dig Liver Dis, 2006, 38 (10) :781-782.

[35]HIRSCHFIELD GM, GERSHWIN ME.The immunobiology and pathophysiology of primary biliary cirrhosis[J].Annu Rev Pathol, 2013, 8 (8) :303-330.

[36]WANG J, BUDAMAGUNTA MS, VOSS JC, et al.Antimitochondrial antibody recognition and structural integrity of the inner lipoyl domain of the E2 subunit of pyruvate dehydrogenase complex[J].JImmunol, 2013, 191 (5) :2126-2133.

[37]LYU J, TAO YY, LIU CH.The characteristics and progress of primary biliary cirrhosis animal model[J].Chin J Gastroenterol Hepatol, 2009, 18 (7) :584-586. (in Chinese) 吕靖, 陶艳艳, 刘成海, 等.原发性胆汁性肝硬化的动物模型特点与研究进展[J].胃肠病学和肝病学杂志, 2009, 18 (7) :584-586.

施引文献

资源附件(0)

访问统计