Research advances in the role of coagulation factors in liver fibrosis
-
摘要: 目前包括肝脏在内的器官纤维化的研究发现,凝血因素和炎症反应共同促进了脏器纤维化的进展,使人们认识到凝血因素的变化不仅仅是肝纤维化的继发性事件,其在肝纤维化的发生发展中,起到了重要的参与作用。总结近年的相关研究发现具有血栓倾向的因子多促进肝纤维化,而具有出血或溶血倾向的因子多抑制肝纤维化。应用抗凝治疗,能明显改善纤维化进展情况。因此应用抗凝治疗或许能为未来肝纤维化提供治疗方向。综述了目前国内外关于凝血因素在肝纤维化中的作用。Abstract: Present studies on organ fibrosis including liver fibrosis show that coagulation factors and inflammatory response promote the progression of organ fibrosis, which makes people to be aware of the fact that the change in coagulation factors is not only a secondary event to liver fibrosis, and coagulation factors also play an important role in the development and progression of liver fibrosis. Recent studies have shown that most of the coagulation factors with thrombotic tendency promote liver fibrosis, while those with bleeding or hemolytic tendency inhibit liver fibrosis. Anticoagulant therapy can significantly improve or alleviate liver fibrosis, and therefore, it may provide a direction for the treatment of liver fibrosis in future. This article reviews the research advances in the role of coagulation factors in liver fibrosis.
-
Key words:
- liver cirrhosis /
- coagulation factors /
- inflammation /
- review
-
[1]SAXENA NK, ANANIA FA.Adipocytokines and hepatic fibrosis[J].Trends Endocrinol Metab, 2015, 26 (3) :153-161. [2]LEONARDI F, MARIA N, VILLA E.Anticoagulation in cirrhosis:A new paradigm?[J].Clin Mol Hepatol, 2017, 23 (1) :13-21. [3]WANLESS IR, WONG F, BLENDIS LM, et al.Hepatic and portal vein thrombosis in cirrhosis:Possible role in the development of parenchymal extinction and portal hypertension[J].Hepatology, 1995, 21 (5) :1238-1247. [4]JAIRATH V, BURROUGHS AK.Anticoagulation in patients with liver cirrhosis:Complication or therapeutic opportunity?[J].Gut, 2013, 62 (4) :479-482. [5]SEKI E, SCHWABE RF.Hepatic inflammation and fibrosis:Functional links and key pathways[J].Hepatology, 2015, 61 (3) :1066-1079. [6]HELLEBRAND C, WILKENS G, KOHL J, et al.Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans[J].Nat Genet, 2005, 37 (8) :835-843. [7]TRIPODI A, PRIMIGNANI M, CHANTARANGKUL V, et al.An imbalance of pro-vs anti-coagulation factors in plasma from patients with cirrhosis[J].Gastroenterology, 2009, 137 (6) :2105-2111. [8]SIMONETTO DA, YANG HY, YIN M, et al.Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces[J].Hepatology, 2015, 61 (2) :648-659. [9]CHAMBERS RC.Abnormal wound healing responses in pulmonary fibrosis:Focus on coagulation signalling[J].Eur Respir Rev, 2008, 17 (109) :130-137. [10]OWENS AP, MACKMAN N.Tissue factor and thrombosis:The clot starts here[J].Thromb Haemost, 2010, 104 (3) :432-439. [11]RAUTOU PE, TATSUMI K, ANTONIAK S, et al.Hepatocyte tissue factor contributes to the hypercoagulable state in a mouse model of chronic liver injury[J].J Hepatol, 2016, 64 (1) :53-59. [12]MOCHIDA S, ARAI S, YAMANOBE F, et al.Anticoagulant targeting for hepatic sinusoidal walls in prevention of hypercoagulopathy in cold preserved rat livers[J].Transplant Proc, 1998, 30 (1) :45-48. [13]CALVARUSO V, MAIMONE S, GATT A, et al.Coagulation and fibrosis in chronic liver disease[J].Gut, 2008, 57 (12) :1722-1727. [14]CAMERER E, HUANG W, COUGHLIN SR.Tissue factor-and factor X-dependent activation of protease-activated receptor 2 by factor VIIa[J].Proc Natl Acad Sci U S A, 2000, 97 (10) :5255-5260. [15]NAULT R, FADER KA, KOPEC AK, et al.From the cover:Coagulation-driven hepatic fibrosis requires protease activated receptor-1 (PAR-1) in a mouse model of TCDD-elicited steatohepatitis[J].Toxicol Sci, 2016, 154 (2) :381-391. [16]KITASATO L, YAMAOKA-TOJO M, HASHIKATA T, et al.Factor Xa in mouse fibroblasts may induce fibrosis more than thrombin[J].Int Heart J, 2014, 55 (4) :357-361. [17]HOWELL DCJ, GOLDSACK NR, MARSHALL RP, et al.Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis[J].Am J Pathol, 2001, 159 (4) :1383-1395. [18]BORENSZTAJN K, von der THUSEN, JAN H, et al.The coagulation factor Xa/protease activated receptor-2 axis in the progression of liver fibrosis:A multifaceted paradigm[J].J Cell Mol Med, 2010, 14 (1-2) :143-153. [19]FIORUCCI S, ANTONELLI E, DISTRUTTI E, et al.PAR1 antagonism protects against experimental liver fibrosis.Role of proteinase receptors in stellate cell activation[J].Hepatology, 2004, 39 (2) :365-375. [20]RUPPERT C, MARKART P, WYGRECKA M, et al.Role of coagulation and fibrinolysis in lung and renal fibrosis[J].Hamostaseologie, 2008, 28 (1-2) :30-36. [21]ATKINSON JM, PULLEN N, Da SILVA-LODGE M, et al.Inhibition of thrombin-activated fibrinolysis inhibitor increases survival in experimental kidney fibrosis[J].J Am Soc Nephrol, 2015, 26 (8) :1925-1937. [22]MERCER PF, CHAMBERS RC.Coagulation and coagulation sig-nalling in fibrosis[J].Biochim Biophys Acta, 2013, 1832 (7) :1018-1027. [23]HOEKSTRA J, GUIMARAES AH, LEEBEEK FW, et al.Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome[J].Blood, 2010, 115 (2) :388-395. [24]BORENSZTAJN K, CONG L, FRANCOIS C, et al.Coagulation factor IX deficiency does not afford protection from pulmonary fibrosis in the experimental murine bleomycin model[J].Eur Respir J, 2012, 40:3670. [25]WILBERDING JA, PLOPLIS VA, MCLENNAN I, et al.Development of pulmonary fibrosis in fibrinogen-deficient mice[J].Ann N Y Acad Sci, 2001, 936 (1) :542-548. [26]RAMACHANDRAN R, NOORBAKHSH F, DEFEA K, et al.Targeting proteinase-activated receptors:Therapeutic potential and challenges[J].Nat Rev Drug Discov, 2012, 11 (1) :69-86. [27]CHAMBERS RC.Role of coagulation cascade proteases in lung repair and fibrosis[J].Eur Respir J, 2003, 22 (44) :33-35. [28]MARIA ME, MAR A TM, ANTONIO JRA, et al.Inflammatory status in human hepatic cirrhosis[J].World J Gastroenterol, 2015, 21 (41) :11522-11541. [29]SENZOLO M, M SARTORI T, ROSSETTO V, et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosistemic shunt for the management of portal vein thrombosis in cirrhosis[J].Liver Int, 2012, 32 (6) :919-927. [30]CERINI F, VILASECA M, LAFOZ E, et al.Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats[J].J Hepatol, 2016, 64 (4) :834-842. [31]WANG BY, ZHAO W, NIU XM, et al.Mechanism of action of Yiqi Huoxue Recipe in regulating autophagy and reversing liver fi-brosis[J].Chin J Hepatol, 2017, 25 (5) :365-370. (in Chinese) 王宝玉, 赵文, 牛学敏, 等.益气活血方调节自噬及逆转肝纤维化机制的研究[J].中华肝脏病杂志, 2017, 25 (5) :365-370. [32]XIE XC, LIU MH, ZHAO SH, et al.Assessment of therapeutic effect of nuemu pill in the hepatitis-B liver fibrosis[J].J Changchun Univ Chin Med, 2016, 32 (1) :123-125. (in Chinese) 谢湘春, 刘明晖, 赵树华, 等.疟母丸治疗乙型肝炎肝纤维化的效果[J].长春中医药大学学报, 2016, 32 (1) :123-125. [33]LI WC, ZHANG JS, ZHU HG, et al.Effect of low anticoagulative activity heparin on the growth of rat hepatic stellate cells[J].J Zhengzhou Univ:Med Sci, 2007, 42 (3) :451-453. (in Chinese) 李文才, 张锦生, 朱虹光, 等.低抗凝肝素对大鼠肝星状细胞生长的影响[J].郑州大学学报:医学版, 2007, 42 (3) :451-453. [34]LI CJ, YANG ZH, SHI XL, et al.Effects of aspirin and enoxaparin in a rat model of liver fibrosis[J].World J Gastroenterol, 2017, 23 (35) :6412-6419. [35]YAN YS, GUAN CG, DU SS, et al.Effects of enzymatically depolymerized low molecular weight heparins on CCl4-induced liver fibrosis[J].Front Pharmacol, 2017, 8:514.
本文二维码
计量
- 文章访问数: 1335
- HTML全文浏览量: 52
- PDF下载量: 354
- 被引次数: 0