肝纤维化药物治疗的新进展

马振增; 陆伦根

doi:10.3969/j.issn.1001-5256.2016.06.039

肝纤维化药物治疗的新进展

DOI: 10.3969/j.issn.1001-5256.2016.06.039

上海交通大学附属第一人民医院消化科

详细信息

中图分类号: R575.2
计量
- 文章访问数: 2784
- HTML全文浏览量: 60
- PDF下载量: 661
- 被引次数: 0
出版历程
- 出版日期: 2016-06-20

New advances in drug therapies for liver fibrosis

摘要

摘要: 各种病因造成肝纤维化的发病率和病死率在全世界范围内居高不下,并呈逐年增高的趋势,目前除了肝移植尚无行之有效的可以根治肝纤维化的方法,并且其产生的严重并发症威胁患者的健康,并造成严重的医疗负担,因此迫切需要有效的抗纤维化药物。近年抗肝纤维化药物的研发及治疗取得了显著的进展,针对肝纤维化的不同靶点、抑制肝星状细胞活化与增殖、增强基质金属蛋白酶活性及抑制金属蛋白酶组织抑制剂的活性、抑制炎症反应、调节免疫反应的药物及中药,以及纳米颗粒与抗纤维化药物结合的治疗和基因治疗的进展进行了综述。
- 肝硬化 /
- 药物治疗 /
- 综述
Abstract: The morbidity and mortality of liver fibrosis induced by a variety of causes remain high around the world and tend to increase year by year.At present,there are no effective radical treatments for liver fibrosis except liver transplantation,and the serious complications of liver fibrosis greatly threaten patients' health and cause a heavy medical burden.Therefore,effective drugs are needed to fight against liver fibrosis.In recent years,great achievements have been made in the research and development of anti- fibrotic drugs and the treatment of liver fibrosis.This article reviews the research advances in drugs and traditional Chinese medicines which act on the different targets of liver fibrosis,inhibit the activation and proliferation of hepatic stellate cells,enhance the activity of matrix metalloproteinase and inhibit the activity of tissue inhibitor of metalloproteinase(TIMP),inhibit inflammatory response,and regulate immune response,as well as the combination of nanoparticles and anti- fibrotic drugs and gene therapy for liver fibrosis.
- liver cirrhosis /
- drug therapy /
- review

HTML全文

参考文献(34)

[1]KIM DC,JUN DW,LEE KN,et al.5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis[J].Liver Int,2013,33(4):535-543.

[2] WANG PP,XIE DY,LIANG XJ,et al.HGF and direct mesenchymal stem cells contact synergize to inhibit hepatic stellate cells activation through TLR4/NF-k B pathway[J].PLo S One,2012,7(8):e43408.

[3]ZHU YW,GONG L,WU GJ,et al.An experimental study on in vitro transfection of mesenchymal stem cells with knocking-out TIMP-1gene by HIV-based lentiviral in rats[J].Jiangsu Med J,2015,41(11):1258-1260.(in Chinese)朱颖炜,龚镭,吴高珏,等.TIMP-1-shRNA基因体外转染大鼠骨髓间充质干细胞的实验研究[J].江苏医药,2015,41(11):1258-1260.

[4] LIU J,CHENG X,GUO Z,et al.Truncated active human matrix metalloproteinase-8 delivered by a chimeric adenovirus-hepatitis B virus vector ameliorates rat liver cirrhosis[J].PLo S One,2013,8(1):e53392.

[5]WANG Y,GAO J,ZHANG D,et al.New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis[J].Hepatol,2010,53(1):132-144.

[6]MARLAKA JR,PAPADOGIANNAKIS N,FISCHLER B,et al.Tacrolimus without or with the addition of conventional immunosuppressive treatment in juvenile autoimmune hepatitis[J].Acta Paediatrica,2012,101(9):993-999.

[7]PETRASEK J,DOLGANIUC A,CSAK T,et al.Interferon regulatory factor 3 and typeⅠinterferons are protective in alcoholic liver injury in mice by way of crosstalk of parenchymal and myeloid cells[J].Hepatology,2011,53(2):649-660.

[8] KIM KA,JEONG SH.The diagnosis and treatment of primary biliary cirrhosis[J].Kor J Hepatol,2011,17(3):173-179.

[9]PENG TS,LIU YZ,YU GF.Efficacy of antioxidant N-acetylcysteine in treatment of chronic hepatitis B fibrosis[J].Guangdong Med J,2013,34(6):948-951.(in Chinese)彭土生,刘英姿,余桂芳.抗氧化剂N-乙酰半胱氨酸治疗慢性乙型肝炎肝纤维化的疗效[J].广东医学,2013,34(6):948-951.

[10] LAVINE JE,SCHWIMMER JB,van NATTA ML,et al.Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents:the TONIC randomized controlled trial[J].JAMA,2011,305(16):1659-1668.

[11]MITANI Y,IWANAGA T,NABESHIMA T,et al.Superoxide scavenging activity of pirfenidone-iron complex[J].Biochem Biophys Res Commun,2008,372(1):19-23.

[12] FNA X,ZHANG Q,LV Y,et al.Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1[J].PLo SOne,2013,8(12):e82190.

[13]YU DK,GAO Y,ZHANG CX,et al.Whole genome analysis of the effect of retinoic acid on liver fibrosis[J].Chin Pharmacol Bull,2013,29(9):1213-1216.(in Chinese)喻冬柯,高塬,张彩霞,等.全基因表达谱分析维甲酸对大鼠肝纤维化的影响[J].中国药理学通报,2013,29(9):1213-1216.

[14] FLORES-CONTRERAS L,SANDOVAL-RODRGUEZ AS,ME-NA-ENRIQUEZ MG,et al.Treatment with pirfenidone for two years decreases fibrosis,cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C[J].BMC Gastroenterol,2014,14(1):131.

[15] SRIRAM S,ROBINSON P,PI L,et al.Triple combination of siR-NAs targeting TGFβ1,TGFβR2,and CTGF enhances reduction of collagen 1 and smooth muscle actin in corneal fibroblasts[J].Invest Ophthalmol Vis Sci,2013,54(13):8214-8223.

[16] MICHAL CN,SCOTT LF.Current status of novel antifibrotic therapies in patients with chronic liver disease[J].Ther Adv Gastroenterol,2011,4(6):391-417.

[17] GARMEL BN,SEBLE L,JACK G,et al.Dissecting fibrosis:therapeutic insights from the small-molecule toolbox[J].Nat Rev Drug Discov,2015,14(10):693-720.

[18]HONG F,CHOU H,FIEL MI,et al.Antifibrotic activity of sorafenib in experimental hepatic fibrosis:refinement of inhibitory targets,dosing,and window of efficacy in vivo[J].Dig Dis Sci,2013,58(1):257-264.

[19] BARRY-HAMILTON V,SPANGLER R,MARSHALL D,et al.Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment[J].Nat Med,2010,16(9):1009-1017.

[20] KING TE,BRADFORD WZ,CASTRO-BERNARDINI S,et al.A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis[J].N Engl J Med,2014,370(22):2083-2092.

[21] NANTHAKUMAR CB,LEMMA S,GAULDIE J,et al.Dissecting fibrosis:therapeutic insights from the small-molecule toolbox[J].Nat Rev Drug Discov,2015,14(10):693-720.

[22] KULKARNI AA,THATCHER TH,OLSEN KC,et al.PPAR-γligands repress TGF-β-induced myofibroblast differentiation by targeting the PI3k/Akt pathway:implications for therapy of fibrosis[J].PLo S One,2011,6(1):e159009.

[23] SON MK,RYU YL,JUNG KH,et al.HS-173,a novel PI3K inhibitor,attenuates the activation of hepatic stellate cells in liver fibrosis[J].Scientif Rep,2013,3(12):3470.

[24] EVA H,SHINOBU MA,ULRIKE H,et al.Synthetic farnesoid Xreceptor agonists induce high-density lipoprotein-mediated transhepatic cholesterol efflux in mice and monkeys and prevent atherosclerosis in cholesteryl ester transfer protein transgenic low-density lipoprotein receptor(-/-)mice[J].J Pharmacol Exp Ther,2012,343(3):556-567.

[25]GIANNITRAPANI L,SORESI M,BONDML,et al.Nanotechnology applications for the therapy of liver fibrosis[J].World J Gastroenterol,2014,20(23):7742-7251.

[26]ADRIAN JE,KAMPS JA,MEIJER DK,et al.A novel lipidbased drug carrier targeted to the non-parenchymal cells,including hepatic stellate cells,in the fibrotic livers of bile duct ligated rats[J].Biochim Biophys Acta,2007,1768(6):1430-1439.

[27]PATEL G,KHER G,MISRA A.Preparation and evaluation of hepatic stellate cell selective,surface conjugated,peroxisome proliferator-activated receptor-gamma ligand loaded liposomes[J].JDrug Target,2012,20(20):155-165.

[28]WAGN Q,WANG H,RAO L,et al.Influence of RNAi-mediated adenosine A1 and A2A receptor gene silencing on acetaldehydeinduced activation and proliferation of hepatic stellate cells in rats[J].Chin Pharmacol Bull,2015,31(1):50-55.(in Chinese)王琪,王和,饶玲,等.RNAi介导大鼠腺苷A1和A2A受体基因沉默对乙醛诱导的肝星状细胞活化增殖的影响[J].中国药理学通报,2015,31(1):50-55.

[29] KWIECINSKI M,ELFIMOVA N,NOETEL AT,et al.Expression of platelet-derived growth factor-C and insulin-like growth factorⅠin hepatic stellate cells is inhibited by miR-29[J].Lab Invest,2012,92(7):978-987.

[30]WANG JS,SUN GZ,CHEN LY,et al.Chinese medicine understanding of liver fibrosis[J].Jilin J Tradit Chin Med,2015,35(5):533-536.(in Chinese)王靖思,孙桂芝,陈兰羽,等.肝纤维化中医认识[J].吉林中医药,2015,35(5):533-536.

[31]WANG R,PAN P,WANG YJ,et al.Effects of salvianolate on expression of NF-k B and Ik Bαin rats with liver fibrosis[J].Chinese J New Drugs Clin Rem,2011,30(1):51-52.(in Chinese)王蓉,潘沛,王彧杰,等.丹参多酚酸盐对纤维化大鼠NF-κB和Ik Bα表达的影响[J].中国新药与临床杂志,2011,30(1):51-52.

[32] CHEN SR,ZOU LY,LI L,et al.The protective effect of glycyrrhetinic acid on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2[J].PLo S One,2013,8(1):53662-53665.

[33]YANG FR,FANG BW,LOU JS.Effects of fufang biejia ruangan pillson hepatic fibrosis in vivo and in vitro[J].World J Gastroenterol,2014,19(32):5326-5333.

[34] TAO YY,YAN XC,ZHOU T,et al.Fuzheng huayu recipe alleviates hepatic fibrosis via inhibiting TNF-αinduced hepatocyte apoptosis[J].BMC Complement Altern Med,2014,14(1):1-13.

施引文献

资源附件(0)

访问统计