期刊文献+

复方鳖甲软肝片抗肝纤维化机制的实验研究 被引量:104

An experimental study on the mechanism of anti-hepatic fibrosis with Chinese medicinal herbs Fufangbiejiaruanganpian
下载PDF
导出
摘要 目的 研究复方鳖甲软肝片 (FFBJRGP)抗肝纤维化作用机制 ,为FFBJRGP的临床应用及抗肝纤维化药物的研发提供参考。方法 应用Chevallier半定量计分系统、酶图法、免疫组织化学、核酸原位杂交及图像分析等技术方法 ,系统观测高、中、低剂量FFB JRGP治疗CCl4诱导肝纤维化模型后各时间段肝组织内关键性纤维化指标的变化 ,包括主要细胞外基质 (ECM)蛋白、基质金属蛋白酶(MMPs)及其抑制剂(TIMPs)表达量及酶活性 ,肝星状细胞 (HSC)的活化与增殖状况 ,以及MMP和膜型MMP(MT MMP)mRNA的表达等。结果 与对照组比较 ,不同剂量FFBJRGP治疗 3个月、6个月结束时及停药后 3个月和 6个月肝组织Chevallier纤维化评分均明显减少(P <0 0 1或P <0 0 5 )。各观察时间段肝组织内TIMP 1和TIMP 2表达量不同程度减少 ,其中高、中治疗剂量组于治疗 3个月结束时降至最低 ,而MMP 2、MMP 13酶降解活性达高峰 ,并维持较高水平至停药后 3个月 ,MMPs和MT MMPs酶蛋白及mRNA表达明显上调 ,肝组织内TGF β1及其mRNA表达、α SMA阳性HSC数量显著减少 ;Ⅰ、Ⅲ、Ⅳ型胶原降解幅度与MMPs及MT MMPs表达量及酶活性大致呈平行关系。 Objective To study the effect of the traditional Chinese medicinal herbs, Fufangbiejiaruanganpian (FFBJRGP), in an experimental model of hepatic fibrosis and its pharmacodynamics. Methods An experimental model of hepatic fibrosis induced by carbon tetrachloride in rat was reproduced, and FFBJRGP was given in high, moderate, and low dosage for 0, 1, 3 and 6 months respectively. Six months after the treatment, matrix metalloproteinase MMP-2, MMP-13, MT-MMP-1, MT-MMP-2 and their inhibitor TIMP-1 and TIMP-2, total extracellular matrix and collagen I, Ⅲ and Ⅳ, and active hepatic stellate cells in the fibrotic livers were qualitatively and quantitatively examined at the protein and/or mRNA expression levels by using immunohistochemistry, in situ hybridization, image analysis and Chevallier's scoring system. Meanwhile, enzyme-degrading activities of MMP-2 and MMP-13 were assessed with gelatin or collagen substrate zymography respectively. Results Compared with the control group, in which rats with hepatic fibrosis were not treated with FFBJRGP, the histological examination of rat livers in the treatment groups showed that the total scores of hepatic fibrosis in treatment groups with varions dosage were significantly decreased 3,6 months after the treatment and 3,6 months after the termination of treatment (P<0.01 or 0.05 respectively). The reduction in TIMP-1 and TIMP-2, obviously elevated enzyme-degrading activities and up-regulated expression of MMPs at protein and mRNA levels were found in the liver tissues of the FFBJRGP treatment groups, and the effect approached the peak 3 months after treatment. The activation and proliferation of HSC, and TGF-β 1 expression were suppressed. ECM degradation was generally parallel to the changes in MMPs. Conclusion The results suggested that FFBJRGP might affect several key steps in the process of hepatic fibrosis and possess multi-drug effect targets for treatment of liver fibrosis.
出处 《解放军医学杂志》 CAS CSCD 北大核心 2004年第7期560-562,共3页 Medical Journal of Chinese People's Liberation Army
基金 国家自然科学基金资助课题 (编号 30 1 30 2 2 0 )
关键词 肝硬化 植物 药用 机制 实验 liver cirrhosis plants, medicinal mechanism experiment
  • 引文网络
  • 相关文献

参考文献9

  • 1赵景民,张月娥.Ito细胞在大鼠实验性肝硬变中的动态研究[J].中华病理学杂志,1991,20(2):91-94. 被引量:13
  • 2[2]Chevallier M.A histological SSS for evaluation of hepatic fibrosis in needle liver biopsy specimens: Comparison with morphometric studies.Hepatology,1994,20(4):349
  • 3赵景民,翟为溶,张月娥,周筱梅,朱虹光,张锦生.人肝细胞癌中整合素α5、β1亚基和纤维连接蛋白mRNAs的表达[J].中华病理学杂志,1998,27(2):94-98. 被引量:11
  • 4[4]Gogly B,Groult N,Hornebeck W et al.Collagen zymography as a sensitive and specific technique for the determination of subpicogram levels of interstitial collagenase.Anal Biochem,1998,255(2):211
  • 5[5]Brown PD,Bloxidge RE,Anderson E et al.Expression of activated gelatinase in human invasive breast carcinoma.Clin Exp Metastasis,1993,11(2):183
  • 6[6]Arthur MJP.Fibrosis Ⅱ.Metalloproteinases and their inhibitors in liver fibrosis.Am J Physiol Gastrointest Liver Physiol,2000,279:G245
  • 7[7]Vaillant B,Chiaramonte MG,Cheever AW et al.Regulation of hepatic fibrosis and extracellular matrix genes by the th response: new insight into the role of tissue inhibitors of matrix metalloproteinases.J Immunol,2001,167(12):7017
  • 8[8]Benyon RC,Arthur MJ.Extracellular matrix degradation and the role of hepatic stellate cells.Semin Liver Dis,2001,21(3):373
  • 9[9]Tsukamoto H.Cytokine regulation of hepatic stellate cells in liver fibrosis.Alcohol Clin Exp Res,1999,23(5):911

二级参考文献3

  • 1张月娥,中华病理学杂志,1985年,14卷,95页
  • 2Chen L B,Cell,1977年,10卷,393页
  • 3赵景民,中华病理学杂志,1997年,26卷,65页

共引文献22

同被引文献778

引证文献104

二级引证文献791

;
使用帮助 返回顶部