Paper - WANFANG MED ONLINE

You Position: Home > Paper

Effects of TNFa, IL-6 and IL-10 on the development of experimental rat liver fibrosis

( views:285, downloads:29 )

Author:: No author available

Journal Title:: WORLD CHINESE JOURNAL OF DIGESTOLOGY

Issue:: 11

DOI:: 10.3969/j.issn.1009-3079.2001.11.004

Key Word:: 肝硬化,实验性/病理生理学;肿瘤坏死因子;白介素6;白介素10

Abstract：目的探讨TNF-α,IL-6及IL-10在实验性大鼠肝纤维化进程中的作用.方法清洁级♂SD大鼠100只,随机分为3组.正常对照组(c组)24只,腹腔内注射生理盐水2mL·kg-1,2次·wk-1;模型组(M组)40只及治疗组(T组)36只,腹腔内注射500mL·kg-1CCl4,2mL·kg-1,2次·wk;E组从3wk起,注射CCl4前腹腔内注射IL-10 4ug·kg.于5wk,7wk,9wk分别随机选取C组动物7只,M,E组动物各10只颈动脉插管取血,留取肝脏,ELISA法测定血清中TNF-a,IL-6及IL-10水平,肝脏常规石蜡切片,银染.结果肝脏病理组织学检查证实成功构建CCl4诱导的实验性大鼠肝纤维模型,且随注射CCl4次数增多,肝纤维化程度逐渐加重,同时期动物T组较M组肝纤维化程度减轻.c组血清TNF-a、IL-6及IL-10水平分别为(15.2±3.8)ng·L-1,(63.6±33.0)ng·L-1和(132 9±22.1)ng·L-1;M组水平分别为(18.9±5.3)ng·L-1,(89.1±25.4)ng·L-1和(57.6±18.9)ng·L-1;T组水平分别为(14.0±1.9)ng·L-1,(74 7±21.2)ng·L-1及(88.2±20.8)ng·L-1.wk5,7,9,M组TNF-a动态变化水平分别为(16.5±2.7)ng·L-1,(17.1±0.9)ng·L-1,(22.6±6.8)ng·L-1;T组水平分别为(13.4±1.0)ng·L-1,(13.6±1.2)ng·L-1,(14.5±2.9)ng·L-1;M组IL-6动态变化水平分别为(63 8±12.2)ng·L-1,(7l 5±16 1)ng·L-1,(112.3±20 2)ng·L-1,T组水平分另4为(63.1±13.1)ng·L-1,(70.1±11.8)ng·L-1,(85.8±11.6)ng·L-1;M组IL-10动态变化水平分别为(82.1±5.2)ng·L-1,(65.7±8.4)ng·L-1,(50 0±8.5)ng·L-1.M组TNF-a及IL-6水平显著高于c组和T组(P<0.05),且在肝纤维化进程中呈动态上升趋势,经IL-10干预后,二者水平下降与M组有明显差异(P<0.05)M组IL-10水平低于N组(P<0.05),在肝纤维化进程中呈动态下降趋势.结论TNF-a,II-6升高及IL-10降低在肝纤维化进程中起重要促进作用,予以外源性IL-10对CCl4诱导的肝纤维化有明显拮抗作用.

Reference

[1]张莉娟,王小众.液递物质与门静脉高压症[J].2000,(11).
[2]Thompson,K,Maltby,J,Fallowfield,J,etc.Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis (see comments)[J].1998,28(6).
[3]H Sprenger,A Kaufmann,H Garn,etc.Induction of neutrophil-attracting chemokines in transforming rat hepatic stellate cells[J].1997,113(1).
[4]Desmouliere A,Lepreux S,Balabaud C,etc.Activation of cultured rat hepatic stellate cells by tumoral hepatocytes.[J].1999,79(4).
[5].Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 Expression in Fibrotic Rat Liver[J].2000,(6).
[6]Beg, Amer A.,Baltimore, David.An essential role for NF-kappaB in preventing TNF-alpha-induced cell death.[J].1996,274(5288).
[7]Michael I. Luster,Dori R. Germolec,Takahiko Yoshida,etc.Endotoxin-induced cytokine gene expression and excretion in the liver[J].1994,19(2).
[8]Wang SC,Schrum L,Tsukamoto H,etc.Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells.[J].1998,273(1).
[9]T, Kasama,R M, Strieter,N W, Lukacs,etc.Regulation of neutrophil-derived chemokine expression by IL-10.[J].1994,152.
[10]H, Tsukamoto.Cytokine regulation of hepatic stellate cells in liver fibrosis.[J].1999,23(5).
[11]L, Llorent,Y, Richaud-Patin,N, Alcocer-Castillejos,etc.Cytokine gene expression in cirrhotic and non-cirrhotic human liver.[J].1996,24(5).
[12]K C, Thompson,A, Trowern,A, Fowell,etc.Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation In vitro.[J].1998,28.
[13]Knittel T.Transforming growth factor\u03b21-regulated gene expression of Ito cells[J].1996.
[14]H Louis,O Le Moine,MO Peny,etc.Hepatoprotective role of interleukin 10 in galactosamine/lipopolysaccharide mouse liver injury[J].1997,112(3).
[15]Gressner AM,Sprenger H,Garn H,etc.Differential expression of monocyte chemotactic protein-1 (MCP-1) in transforming rat hepatic stellate cells.[J].1999,30(1).
[16]Cun-Yu Wang,Marty W. Mayo,Robert G. Korneluk,etc.NF-κB Antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation[J].1998,281 (5383).
[17]Tsukamoto,H.Is interleukin-10 antifibrogenic in chronic liver injury? (editorial; comment)[J].1998,28(6).
[18]Takemura M,Ishikawa T,Moriwaki H,etc.Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A.[J].1999,11(9).
[19]Michael Seitz,Pius Loetscher,Beatrice Dewald,etc.Interleukin-10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts[J].1995,25(4).
[20]YU Yan-Yan,SI Chong-wen,TIAN Xiu-lan,etc.Effect of cytokines on liver necrosis[J].1998,(4).
[21]Taub,R.Blocking NF-kappaB in the liver: the good and bad news (editorial; comment)[J].1998,27(5).
[22]D R, Nelson,G Y, Lauwers,J Y, Lau,etc.Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: a pilot trial of interferon nonresponders.[J].2000,118(4).
[23]Koziel MJ.Cytokines in viral hepatitis.[J].1999,19(2).
[24]D E, Cressman,L E, Greenbaum,R A, DeAngelis,etc.Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice.[J].1996,274.
[25]Moshage H.Cytokines and the hepatic acute phase response.[J].1997,181(3).
[26]Christ B,Ramadori G.Cytokines and the hepatic acute-phase response.[J].1999,19(2).
[27]Wu P,Wang P,Egan RW,etc.Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms.[J].1995,270(16).
[28]P, Greenwel,M, Rojkind.Accelerated development of liver fibrosis in CCl4-treated rats by the weekly induction of acute phase response episodes: upregulation of alpha1(I) procollagen and tissue inhibitor of metalloproteinase-1 mRNAs.[J].1997,1361.