期刊文献+

大鼠胆管梗阻后肝脏纤维化相关细胞因子的变化

Changes in expression of hepatic fibrosis related cell factors in rats with bile duct obstruction
下载PDF
导出
摘要 目的:通过结扎大鼠胆总管,模拟胆管梗阻病理状态,运用PCR技术,探讨这一病理过程相关细胞因子在胆管梗阻肝脏纤维化过程中发挥的作用.方法:实验组实施近肝门端胆总管单线结扎;对照组实施假手术,开腹游离胆总管但不结扎.术后不同时间处死大鼠,取肝组织通过PCR检测各目的基因表达情况.结果:两组间转化生长因子-β(transforming growth factor-β,TGF-β1)、COL-Ⅰ的表达差异从第1天开始有统计学意义,BDL组与对照组中HGF的表达差异从第3天开始有统计学意义.对BDL不同天数组间的表达研究发现COL-Ⅰ、TGF-β1在3-7 d无统计学意义,HGF在1-3、7-21 d无统计学意义,而其他相邻各组间均有统计学意义,COL-Ⅰ、TGF-β1指标1-3d增长趋势最明显,HGF指标3-7 d增长趋势最明显.结论:肝纤维化过程中的3-7 d是纤维化过程的特殊时期,第3天之前以促纤维化过程为主要表现;第3天开始出现抗纤维化表现,促纤维化趋势减弱,纤维化速度减慢;第7天之后为持续的肝脏纤维化进程. AIM: To explore the roles of cytokines related to the pathological process of biliary obstruction and hepatic fibrosis. METHODS: Rats were divided into two groups: an experimental group and a control group. The experimental group underwent ligation of the common bile duct to induce bile duct obstruction (BDO), and the control group received laparotomy only without ligation. Rats were sacrificed after the operation. Expression of genes of interest was detected by PCR. RESULTS: Expression of COL- I and transforming growth factor-β (TGF-β1) changed significantly from day 1, and that of HGF showed a significant change from day 3. In the BDL group, expression of COL- I and TGF-I showed no significant differences during the period from day 3 to day 7, and that of HGF showed no significant differences during the periods from day 1 to day 3 and from day 7 to day 21, while sta tistically significant differences were observed in other periods. These findings suggest that expression of COL- I and TGF-β1 increased fastest from days 1 to 3, and that of HGF increased fastest from days 3 to 7. CONCLUSION: The findings of the present study suggest that the period before day 3 is a stage of rapid fibrosis, the period between days 3 and 7 is a stage of slow fibrosis, and the period after day 7 is a stage of continuous progression of fibrosis.
出处 《世界华人消化杂志》 CAS 北大核心 2014年第10期1402-1408,共7页 World Chinese Journal of Digestology
基金 国家自然科学基金资助项目 No.81000156~~
关键词 胆管梗阻 肝纤维化 转化生长因子Β1 肝细胞生长因子 I型胶原蛋白 Bile duct obstruction Liver fibrosis Transforming growth factor-β1 HGF COL- I
  • 相关文献

参考文献15

  • 1Yang N, Mahato RI. GFAP promoter-driven RNA interference on TGF-βI to treat liver fibrosis. Pharm Res 2011; 28:752-761 [PMID: 21347569 DOh 10.1007/s11095-011-0384-y].
  • 2Ishikawa H, Jo JI, Tabata Y. Liver Anti-Fibrosis Therapy with Mesenchymal Stem Cells Secreting Hepatocyte Growth Factor. J Biomater Sci Polym Ed 2011 Dec 14. [Epub ahead of print] [PMID: 22182291].
  • 3Iwaisako K, Brenner DA, Kisseleva T. What's new in liver fibrosis? The origin of myofibroblasts in liver fibrosis. J Gastroenterol Hepatol 2012; 27 Suppl 2:65-68 [PMID: 22320919 DOI: 10.1111/ j.1440-1746.2011.07002.x].
  • 4Cong M, Iwaisako K, Jiang C, Kisseleva T. Cell signals influencing hepatic fibrosis. Int J Hepa- tol 2012; 2012:158547 [PMID: 22973518 DOI: 10.1155/2012/158547].
  • 5Tang LX, He RH, Yang G, Tan JJ, Zhou L, Meng XM, Huang XR, Lan HY. Asiatic acid inhibits liver fibrosis by blocking TGF-beta/Smad signaling in vivo and in vitro. PLoS One 2012; 7:e31350 [PMID: 22363627 DOI: 10.1371/journal.pone.0031350].
  • 6Chaivez E, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Castro-Sanchez L, Salazar EP, Moreno MG, Muriel P. Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetra- chloride in the rat. Liver Int 2010; 30:969-978 [PMID: 20524983 DOI: 10.1111/j.1478-3231.2010.02256].
  • 7田卫斌,王胜春,李晓伟,胡咏武,赵辉平.大鼠肝纤维化形成过程中TGF-β1/ERK信号通路与Ⅰ、Ⅲ、Ⅳ型胶原表达变化[J].胃肠病学和肝病学杂志,2010,19(5):414-419. 被引量:6
  • 8Rahimi RA, Leof EB. TGF-beta signaling: a tale of two responses. J Cell Biochem 2007; 102:593-608 [PMID: 17729308].
  • 9Xia JL, Dai C, Michalopoulos GK, Liu Y. Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation. Am J Pathol 2006; 168:1500-1512 [PMID: 16651617].
  • 10Jia C. Advances in the regulation of liver regenera- tion. Expert Rev Gastroenterol Hepato12011; 5:105-121 [PMID: 21309676 DOI: 10.1586/egh.10.87].

二级参考文献15

  • 1Miyazono K. Positive and negative regulation of TGF signaling [ J]. J Cell Sci, 2000, 113(Pt 1) : 1101-1109.
  • 2Dodey S, Delvoux B, Streckert M, et al. Transforming growth factor beta signal transduction in hepatic stellate cell via smad2/3 phosphorylation,a pathway that is abrogated during in vitro progression to myofibroblasts TGF-β signal transduction during Trans-differentiation of hepatic stellate cells [ J]. FEBS Lett, 2001, 502(1-2) : 4-10.
  • 3Davis BH, Chen A, Beno DWA. Raf and mitogen-aetivated protein kinase regulate stellate cell collagen gene expression [ J]. J Biol Chem,1996, 271(3): 11039-11042.
  • 4Hayaashida T, Decaestecker M, Sehnaper HW. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells [ J]. FASEB J, 2003, 17 (11) : 1576-1578.
  • 5Yue J, Mulder KM. Transforming growth factor-beta signal tranbduct in epithelial cells [J]. Pharmacol Ther, 2001, 91 ( 1 ) : 1-34.
  • 6Verrecchla F, Mauviel A. Transforming-growth-factor-beta signaling through the smad pathway: role in extracellular amtrix gene expresion and regulation [J]. J Invest Dermatol, 2002, 118(2) : 211-215.
  • 7Shek FW, Benyon RC. How can transforming growth factor beta be targeted usefully to combat liver fibrosis [ J]. Eur J Gastroenterol Hepatol, 2004, 16(2) : 123-12.
  • 8Tsukada S, Parsons C J, Rippe RA. Mechanisms of liver fibrosis [ J]. Clinic Chimica Acta, 2006, 364(1-2) : 33-60.
  • 9Chen RH, Ebner R, Derynck R. Inactivation of the type Ⅱ receptor reveals two receptor pathway for the diverse TGFβ activity [ J ]. Science, 1993, 260(5112): 1335-1338.
  • 10Datta PK, Mooses HL. Strap and Smad7 synergize in the inhibition of transforming growth factor beta signaling [J]. Mol Cell Biol, 2000, 20(9) : 3156-3157.

共引文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部