期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

肝纤维化能够保护小鼠抵抗D-GalN/LPS诱导的致死性损伤 被引量：1

Liver fibrosis protects mice against lethal injury induced by D-GalN/LPS
下载PDF
导出
摘要 目的:证明四氯化碳(carbon tetrachloride,CCl4)诱导的肝纤维化小鼠对致死性D-氨基半乳糖/脂多糖(D-galactosamine and lipopolysaccharide,D-GalN/LPS)攻击的耐受性.方法:建立CCl4诱导的肝纤维化小鼠模型,于纤维化6 wk时以致死剂量的D-GalN(700 mg/kg)/LPS(50μg/kg)进行攻击,以同样处理的正常小鼠作为对照,即实验共分为4组:正常对照组(Nor)、急性损伤组(Nor+D-GalN/LPS)、肝纤维化组(Fib)、肝纤维化+急性攻击组(Fib+D-GalN/LPS).根据攻击前后小鼠生存率、转氨酶水平及肝组织学的变化来评估正常和纤维化小鼠对致死性D-GalN/LPS损伤的耐受性.结果:生存分析显示,Fib+D-GalN/LPS组的生存率显著高于Nor+D-GalN/LPS组(100%vs20%).血清转氨酶结果表明,Fib+D-GalN/LPS组肝损伤程度明显轻于Nor+D-GalN/LPS组,其sALT水平分别为(6630 U/L±1675 U/L)和(22429 U/L±5446 U/L)(P<0.01).接受攻击的纤维化和正常小鼠的sALT分别升高了14.3倍和455.9倍.肝组织学检查结果也证明,接受致死性D-GalN/LPS攻击的纤维化小鼠的肝损伤较同样处理的正常小鼠明显减轻.结论:CCl4诱导的肝纤维化可保护小鼠抵抗致死性D-GalN/LPS损伤的攻击. AIM： To assess the tolerance of mice with carbon tetrachloride（CCl4）-induced fibrosis to a lethal dose of D-galactosamine/lipopolysaccharide（DGalN/LPS）. METHODS： A mouse model of hepatic fibrosis was established by intraperitoneal injection ofCCl4（in mineral oil）, twice a week for 6 wk. At the end of fibrosis induction, mice were challenged intraperitoneally with D-GalN（700 mg/kg）/LPS（50 μg/kg）. Normal mice treated in the same way were used as controls. Mice were sacrificed 24 h after acute insult. Sera and liver tissues were harvested for analyses. To evaluate the tolerance of normal and fibrotic mice to a lethal dose of D-GalN/LPS, survival rate, serum alanine aminotransferase（sALT） levels and histological changes of the liver were compared between before and after acute challenge.RESULTS： The survival rate of fibrotic mice subjected to a lethal dose of D-GalN/LPS was significantly higher than that of normal mice treated in the same way（100% vs 20%）. After challenged by D-GalN/LPS, sALT in normal mice increased by 455.9 folds（49.2 U/L ± 12.9 U/L vs 22429 U/L ± 5446 U/L, P 0.01）, which was significantly higher than that in fibrotic mice（14.3 folds） [（463.7 U/L ± 109.0 U/L vs 6630 U/L ± 1675 U/L, P 〈0.01）. The tolerance of fibrotic mice to D-GalN/LPS was confirmed by well-preserved liver architecture as compared with controls. CONCLUSION： CCl4-induced liver fibrosis protects mice against a lethal dose of D-GalN/LPS.
作者 白丽 孔明 张晓慧 丁美 郑素军 陈煜 段钟平
机构地区 首都医科大学附属北京佑安医院人工肝中心
出处 《世界华人消化杂志》 CAS 北大核心 2014年第14期1998-2002,共5页 World Chinese Journal of Digestology
基金 国家"十二五"科技重大专项基金资助项目 Nos.2012ZX10002004-006 2012ZX10004904-003-001 2013ZX10002002-006-001 北京市卫生系统高层次卫生技术人才基金资助项目 No.2011-3-083 首都医科大学基础-临床合作基金资助项目 Nos.14JL72 14JL73~~
关键词 肝纤维化 损伤 耐受 Liver fibrosis Lethal injury Tolerance
分类号 R575.2 [医药卫生—消化系统]
  • 相关文献

参考文献19

  • 1Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115:209-218 [PMID: 15690074 DOI: 10,1172/ JCI200524282].
  • 2Friedman SL. Mechanisms of hepatic fibrogen- esis. Gastroenterology 2008; 134:1655-1669 [PMID: 18471545 DOI: 10,1053/j.gastro,2008.03.003].
  • 3Qin L, Han YP. Epigenetic repression of matrix me- talloproteinases in myofibroblastic hepatic stellate cells through histone deacetylases 4: implication in tissue fibrosis. Am J Pathol 2010; 177:1915-1928 [PMID: 20847282 DOI: 10,2353/ajpath,2010,100011].
  • 4Friedman SL. Evolving challenges in hepatic fibro- sis. Nat Rev Gastroenterol Hepatol 2010; 7:425-436 [PMID: 20585339 DOI: 10,1038/nrgastro,2010.97].
  • 5Wynn TA. Fibrotic disease and the T(H)I/T(H)2 paradigm. Nat Rev Immunol 2004; 4:583-594 [PMID: 15286725 DOI: 10,1038/nri1412].
  • 6Friedman SL. Hepatic stellate cells: protean,multifunctional, and enigmatic cells of the liver. Physiol Rev 2008; 88:125-172 [PMID: 18195085 DOI: 10,1152/physrev.00013,2007].
  • 7Wynn TA. Fibrosis under arrest. Nat Med 2010; 16: 523-525 [PMID: 20448575 DOI: 10,1038/nm0510-523].
  • 8Wynn TA. Integrating mechanisms of pulmonary fibrosis. J Exp Med 2011; 208:1339-1350 [PMID: 21727191 DOI: 10,1084/jem,20110551].
  • 9Osawa Y, Hannun YA, Proia RL, Brenner DA. Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver. Hepa- tology 2005; 42:1320-1328 [PMID: 16317686 DOI: 10,1002/hep,20967].
  • 10Osawa Y, Seki E, Adachi M, Suetsugu A, Ito H, Moriwaki H, Seishima M, Nagaki M. Role of acid sphingomyelinase of Kupffer cells in cholestatic liv- er injury in mice. Hepatology 2010; 51:237-245 [PMID: 19821528 DOI: 10,1002/hep,23262].

同被引文献50

  • 1Friedman SL. Liver fibrosis -- from bench to bedside. J Hepato12003; 38 Suppl 1:$38-$53 [PMID: 12591185].
  • 2Su TH, Kao JH, Liu CJ. Molecular mechanism and treatment of viral hepatitis-related liver fibrosis. Int J Mol Sci 2014; 15:10578-10604.
  • 3Nusrat S, Khan MS, Fazili J, Madhoun MF. Cirrhosis and its complications: evidence based treatment. World J Gastroentero12014; 20:5442-5460 [PMID: 24833875 DOI: 10.3748/wjg.v20.i18.5442].
  • 4Zender L, Ht~tker S, Mundt B, Waltemathe M, Klein C, Trautwein C, Malek NP, Manns MP, Kiihnel F, Kubicka S. NFkappaB-mediated upregulation of bel-xl restrains TRAIL-mediated apoptosis in murine viral hepatitis. Hepatology 2005; 41:280-288 [PMID: 15660391 DOI: 10.1002] hep.20566].
  • 5Arthur MJ. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J PhysiolGastrointest Liver Physiol 2000; 279:G245-G249 [PMID: 10915630].
  • 6Marra F. Hepatic stellate cells and the regulation of liver inflammation. J Hepato11999; 31:1120-1130 [PMID: 10604588].
  • 7Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis 2001; 21:311-335 [PMID: 11586463 DOI: 10.1055/s-2001-17550].
  • 8G~ibele E, Brenner DA, Rippe RA. Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell. Front Biosci 2003; 8: d69-d77 [PMID: 12456323].
  • 9Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol 2015; 44-46:247-254 [PMID: 25805621 DOI: 10.1016/j.matbio.2015.03.005].
  • 10Ramirez Correa GA, Zacchigna S, Arsic N, Zentilin L, Salvi A, Sinagra G, Giacca M. Potent inhibition of arterial intimal hyperplasia by TIMPI gene transfer using AAV vectors. Mol Ther 2004; 9:876-884 [PMID: 15194054 DOI: 10.1016/j.ymthe.2004.02.020].

引证文献1

二级引证文献1

世界华人消化杂志
2014年 第14期

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