Sun Xue,Ren Hongxia.Advances in molecular mechanisms of biliary atresia and hepatic fibrosis[J].Journal of Clinical Pediatric Surgery,2019,18(05):432-436.[doi:10.3969/j.issn.1671-6353.2019.05.019]
胆道闭锁发生与肝纤维化的分子机制研究进展
- Title:
- Advances in molecular mechanisms of biliary atresia and hepatic fibrosis
- Keywords:
- Biliary Atresia/ET; Fibrosis; Liver /ET
- 分类号:
- R722.17;R393
- 摘要:
- 胆道闭锁(biliary atresia,BA)的典型表现为肝内外胆管持续性炎症和迅速进展的肝纤维化,目前国内外对于胆道闭锁的病因尚无定论。因此,本文通过查阅、分析、总结近10年来的胆道闭锁相关文献,对胆道闭锁发生及其致肝纤维化的分子机制研究进展作一综述。
- Abstract:
- Biliary atresia (BA) is characterized by persistent internal and external inflammation of bile duct of liver with a rapid progress of liver fibrosis.Today the cause of BS has remained elusive.The occurrence of BS is so complex that various factors play important roles.This review has summarized the relevant literature reports over the last decade.The occurring mechanism,its relationship with various factors and development trends are thoroughly reviewed.
参考文献/References:
1 陈小爱,杨继鑫,冯杰雄.胆道闭锁病因及其发病机制研究进展[J].中华实用儿科临床杂志,2015,30(19):1516-1518.DOI:10.3760/cma.j.issn.2095-428X.2015.19.021.Chen XA,Yang JX,Feng JX.Recent advances of etiology and mechanism of biliary atresia[J].Chin J Appl Clin pediatr,2015,30(19):1516-1518.DOI:10.3760/cma.j.issn.2095-428X.2015.19.021.
2 孟庆娅,詹江华.胆道闭锁病因学研究进展[J].天津医药,2008,36(10):826-827.DOI:10.3969/j.issn.0253-9896.2008.10.033.Meng QY,Zhan JH.Progress in etiology of biliary atresia[J].Tianjin Med J,2008,36(10):826-827.DOI:10.3969/j.issn.0253-9896.2008.10.033.
3 Keplinger KM,Bloomston M.Anatomy and embryology of the biliary tract[J].Surg Clin North Am,2014,94(2):203-217.DOI:10.1016/j.suc.2014.01.001
4 Mukhopadhyay SG,Roy P,Chatterjee U,et al.A histopathological study of liver and biliary remnants in the long-term survivors (>10 years) of cases of biliary atresia[J].Indian J Pathol Microbiol,2014,57(3):380-385.DOI:10.4103/0377-4929.138722.
5 冯杰雄,郑珊.小儿外科学[M].北京:人民卫生出版社,2014:125-128.Feng JX,Zheng S.Pediatric Surgery[M].Beijing:People’s Medical Publishing House,2014:125-128.
6 林海伟,李龙,刁美,等.胆道闭锁Kasai术后近中期疗效及部分影响因素分析[J].中华小儿外科杂志,2013,34(5):388-390.DOI:10.3760/cma.j.issn.0253-3006.2012.01.005.Lin HW,Li L,Diao M,et al.Impact of age at Kasai operation on short/mid-term outcomes of biliary atresia at a single institution[J].Chin J Pediatr Surg,2013,34(5):388-390.DOI:10.3760/cma.j.issn.0253-3006.2012.01.005.
7 Nakamura K,TanoueA.Etiology of biliary atresia as a developmental anomaly recent advances[J].J Hepatobiliary Pancreat Sci,2013,20(5):459-464.DOI:10.1007/s00534-013-0604-4.
8 金祝.胆道闭锁的基因研究进展[J].中华小儿外科杂志,2015,36(8):634-637.DOI:10.3760/cma.j.issn.0253-3006.2015.08.019.Jin Z.Advances in gene research of biliary atresia[J].Chin J Pediatr Surg,2015,36 (8):634-637.DOI:10.3760/cma.j.issn.0253-3006.2015.08.019.
9 Bezerra JA,Tiao G,Ryckman FC,et al.Genetic induction of proinflammatory immunity in children with biliary atresia[J].Lancet,2002,360(9346):1653-1659.DOI:10.1016/s0140-6736(02)11603-5.
10 Shinkai M,Shinkai T,Puri P,et al.Increased CXCR3 expression associated with CD3-positively lmphocytes in the liver and biliary Remnantin biliary atresia[J].J Pediatr Surg,2006,41(5):950-954.DOI:10.1016/j.j ped surg.2006.01.060.
11 Kong YY,Zhao JQ,Wang J,et al.Modified stool color card with digital images was efficient and feasible for early detection of biliary atresia-a pilot study in Beijing,China[J].World Journal of Pediatrics,2016,12(4):415-420.DOI:10.1007/s12519-016-0061-7.
12 Mack CL,Tucker RM,Sokol RJ,et al.Biliarya tresia is associated with CD4+Thl cell-mediated portal tract inflammation[J].PediatrRes,2004,56(1):79-87.DOI:10.1203/01.PDR.0000130480.51066.FB.
13 Takagi K,Yagi T,Shinoura S,et al.Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Liver Transplantation[J].Acta Medica Okayama,2017,71(1):85-89.DOI:10.18926/AMO/54830.
14 Mack CL,Tucker RM,Sokol,et al.Armed CD4+Thl effector cells and activated macrophages participate in bite duct injury in murine biliary atresia[J].Clin Immunol,2005,15(2):200-209.
15 Mack CL,Tucker RM,Lu BR,et al.Cellular and humoral autoimmunit V djrected at bite duct epithelie in murme biliary atresia[J].HepatoIogy,2006,44(5):1231-1239.
16 Brindley SM,Lanham AM,Karrer FM,et al.Cyt Omegal Ovirus-specificT-cell reactivit V in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells[J] Hepato Iogy,2012,55(4):1130-1138.
17 Coots A,Donnelly B,Mohanty SK,et al.Rotavirus infection of human cholangiocytes parallels the murine.
18 Saito T,Hishiki T,Terui K,et al.Toll-like receptor m RNA expression in liver tissue from patients with biliary atresia[J].J Pediatr Gastroenterol Nutr,2011,53(6):620-626.
19 Huang YH,Chou MH,Du YY,et al.Expression of tollIike receptors and type 1 interferon specific protein MxA in biliary atresia[J].Lab Invest,2007,87(1):66-74.
20 陈功,郑珊.新生儿胆道闭锁治疗过程中的常见临床问题[J].临床肝胆病杂志,2015,31(8):1226-1229.DOI:10.3969/j.issn.1001-5256.2015.08.011.Chen G,Zheng S.Common clinical problems during treatment of neonatal biliary atresia[J].J Clin Hepa-tol,2015,31(8):1226-1229.DOI:10.3969/j.issn.1001-5256.2015.08.011.
21 Harada K,Sato Y,Isse K,et al.Induction of innate immune response and absence of subsequent tolerance to dsRNA in biliary epithelial cells relate to the pathogenesis of biliary atresia[J].Liver Int,2008,28(5):614-621.
22 Feldman AG,Tucker RM,Tenner EK,et al.B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia[J].Plo S One,2013,8(8):663-644.
23 朱晓敏.小儿胆道闭锁肝组织MMP-1、MMP-2、内毒素和CD14的表达研究[D].苏州大学,2013.Zhu XM.Expression of MMP-1,MMP-2,endotoxin and CD14 in biliary atresia in children[D].Suzhou Universi-ty,2013.
24 杨瑛,汤绍涛,刘勇军.调节性T细胞、Th17和树突状细胞在胆道闭锁患儿免疫致病机制中的作用[J].中华小儿外科杂志2011,3(10):731-736.DOI:10.3760/cma.j.issn.0253-3006.2011.10.004.Yang Y,Tang ST,Liu YJ,et al.Role of regulation T cells,effect or Th17 and dendritic cells in the progressive inflammatory of biliary atresia[J].Chin J Pediatr Surg,2011,3(10):731-736.DOI:10.3760/cma.j.issn.0253-3006.2011.10.004.
25 王江,郑珊.胆道闭锁免疫失调机制的研究进展[J].中华实用儿科临床杂志,2014,29(17):1342-1345.DOI:10.3760/cma.j.issn.2095-428X.2014.17.016.Wang J,Zheng S.Advances of immunologic dysregulation mechanism in biliary atresia[J].J Chin J Appl Clin pediatr,2014,29(17):1342-1345.DOI:10.3760/cma.j.issn.2095-428X.2014.17.016.
26 彭飞,段栩飞.胆道闭锁发病机制研究进展.[J].临床小儿外科杂志2015,14(1):62-64.DOI:10.3969/j.issn,171-6353,2015.01.018.Peng F,Duan XF.Research advances on the pathogenesis of congenital biliary atresia[J] Clin Ped Sur,2015,14(1):62-64.DOI:10.3969/j.issn,171-6353,2015.01.018.
27 Muraj LT,Mate.Maimicro chimerism in biliary atresia:are maternal cells effector cells,targets or just bystanders[J].Chimerlsm,2014,5(1):1-5.
28 Taylor AW,Kitaichi N.The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy.Brain Behav Immun,2008,22(7):639-646.
29 Murata,K Kamata,Y Munakata,H Sugai,M Sasaki,M.Hepato-gastroenterology,2008,55(81):179-183.
30 王玮,郑珊,沈淳,等.新生儿巨细胞病毒感染与胆道闭锁肝脏纤维化的相关研究[J].中华小儿外科杂志,2005,26(9):464-466.Wang W,Zheng S,Shen C,et al.Relationship between infection of cytomegalovirns and liver fibrosis in biliary atresia[J].Chin J Pediatr Surg,2005,26(9):464-466.
31 Yong T,Xiao J,Wang YW,Chen KJ,Zhou J,Wen Y,Wang Y,Zhou WH,Pan W,Cai Cellular signaling,2014,26(5):925-932.
32 Shivakumar P,Mourya R,Bezerra JA.Perforin and granzy-mes work in synergy to mediate cholangiocyte injury in experimental biliary atresia[J].J Hepatol,2014,60(2):370-376.
33 Banales JM,Masyuk TV,Gradilone SA,et al.The c AMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD).Hepatology,2009,49(2):160-174.
34 Caspary T,Larkins CE,Anderson KV.Graded response to Sonic Hedgehog depends on cilia architecture.Dev Cell,2007,12(10):767-778.
35 Kobayashi H,Horikoshi K,Yamataka A,et al.Are stable postoperative biliary atresia patients really stable[J].Pediat SURG LNT.2001.17(2):104-107.
36 Overall CM,Wrana JL,Sodek J.Transeriptional and posttranseriptional regulation 72-KDa gelatinase/type IV collagenase by transforming growth factor-betal in human fibroblasts:comparisons with collagenase and issue inhibitor of matrix metalloproteinase gene expression[M].J Biol chem,1991,266(11):14064-14071.
37 毛永忠,汤绍涛,阮庆兰.胆道闭锁肝脏组织MMP-2、TGF-β1的表达及意义[J].临床小儿外科杂志2007,6(3):6-9.Mao YZ,Tang ST,Ruan QL,et al.Expressions of MMP-2 and TGF-β1 in liver of biliary atresia and their relations with hepatic fibrosis[J].Clin Ped Sur,2007,17(3):6-9.
38 明安晓,王海斌,林海伟,等.胆道闭锁血清抗α-enolase 自身抗体检测及临床意义[J].中华小儿外科杂志,2012,33(4):263-267.DOI:10.3760/cma.J.issn.0253-3006.2012.04.006.Ming AX,Wang HB,Ling HW,et al.Examination of α-enolase autoantibodies in patients with bilialy atresia[J].Chin J Pediatr Surg,2012,33(4):263-267.DOI:10.3760/cma.J.issn.0253-3006.2012.04.006.
39 Markovics JAl,Araya J,Cambier S.Showing results for increased transcriptional activation of the transforming growth factor-beta-activating integrin subunit beta through altering chromatin architecture[J].J Biol Chem.2011 Oct 21,286(42):64-74.
40 Omenetti A,Diehl AM.Hedgehog signaling in cholangiocytes.Curr Opin Gastroenterol,2011,27:268-275.
41 Chou MH,Chuang JH,Eng HL,et al.Endotoxin and CD14 in the progression of biliary atresia[J].J Transl Med,2010,8(2):138.
42 方燕彬,李索林,徐伟立,等.先天性胆道闭锁发病机制的研究进展[J].中华肝胆外科杂志,2014,20(8):612-616.DOI:10.3760/cma.j.issn.1007-8118.2014.08.01.Fang YB,Li SL,Xu WL,et al.Research advances in the pathogenesis of congenital biliary atresia[J].Chin J Hepatobiliary Surg,2014,20(8):612-616.DOI:10.3760/cma.j.issn.1007-8118.2014.08.01.
相似文献/References:
[1]葛亮,詹江华.胆道闭锁肝纤维化与自体肝生存关系的研究进展[J].临床小儿外科杂志,2020,19(02):171.[doi:10.3969/j.issn.1671-6353.2020.02.016]
Ge Liang,Zhan Jianghua.Relationship between liver fibrosis and native liver survival in infants with biliary atresia[J].Journal of Clinical Pediatric Surgery,2020,19(05):171.[doi:10.3969/j.issn.1671-6353.2020.02.016]
[2]邢晓宇,陈思平,钟量,等.维生素D及其受体与肾盂输尿管连接部狭窄相关性的初步研究[J].临床小儿外科杂志,2020,19(03):209.[doi:10.3969/j.issn.1671-6353.2020.03.004]
Xing Xiaoyu,Chen Siping,Zhong Liang,et al.A preliminary study on the relationship between vitamin D and its receptor and ureteropelvic junction obstruction[J].Journal of Clinical Pediatric Surgery,2020,19(05):209.[doi:10.3969/j.issn.1671-6353.2020.03.004]
[3]卫园园,范晋楠,李亚蕊.ADD3基因rs17095355位点多态性与胆道闭锁相关性研究的Meta分析[J].临床小儿外科杂志,2020,19(06):496.[doi:10.3969/j.issn.1671-6353.2020.06.007]
Wei Yuanyuan,Fan Jinnan,Li Yarui.Meta-analysis of the relationship between single nucleotide polymorphism of rs17095355 and biliary atresia[J].Journal of Clinical Pediatric Surgery,2020,19(05):496.[doi:10.3969/j.issn.1671-6353.2020.06.007]
[4]阿里木江·阿不都热依木,林峰,王皓洁,等.Notch信号通路活化协同巨噬细胞对胆道闭锁肝纤维化的作用研究[J].临床小儿外科杂志,2021,20(04):376.[doi:10.12260/lcxewkzz.2021.04.014]
Alimujiang·Abudureyimu,Lin Feng,Wang Haojie,et al.Activation of Notch signaling pathway collaborated with macrophages for promoting liver fibrosis in biliary atresia[J].Journal of Clinical Pediatric Surgery,2021,20(05):376.[doi:10.12260/lcxewkzz.2021.04.014]
[5]赵一霖,王皓洁,詹江华.胆道闭锁TGFβ1诱导EMT相关通路研究进展[J].临床小儿外科杂志,2021,20(12):1189.[doi:10.12260/lcxewkzz.2021.12.017]
Zhao Yilin,Wang Haojie,Zhan Jianghua.Recent advances of TGFβ1 induced EMT-related signaling pathways in biliary atresia[J].Journal of Clinical Pediatric Surgery,2021,20(05):1189.[doi:10.12260/lcxewkzz.2021.12.017]
[6]黄绍刚,徐瑞,曾椰峰,等.先天性尿路梗阻患儿输尿管组织损伤及功能改变的研究进展[J].临床小儿外科杂志,2025,(02):196.[doi:10.3760/cma.j.cn101785-202401059-017]
Huang Shaogang,Xu Rui,Zeng Yefeng,et al.Research advances in urethral tissue injuries and functional changes in children with congenital urinary tract obstruction[J].Journal of Clinical Pediatric Surgery,2025,(05):196.[doi:10.3760/cma.j.cn101785-202401059-017]
备注/Memo
收稿日期:2017-12-02。
通讯作者:任红霞,Email:renhongxia100@sina.com