Comparison of the Location and Expression of TIMPs between Immune Induced and Toxin Induced Liver Fibrosis Model in Rat
聶青和(Qing-He Nie)；謝玉梅(Yu-Mei Xie)；周永興(Yong-Xing Zhou)；羅新棟(Xin-Dong Luo)；羅紅(Hong Luo)；程勇前(Yong-Qian Cheng)
肝纖維化 ； 免疫誘導型 ； 毒素誘導型 ； 金屬蛋白酶組織抑制因子 ； 動物模型 ； Liver fibrosis ； Toxin induced ； Immune induced ； Tissue inhibitors of metalloproteinase ； Animal model
|Volume or Term/Year and Month of Publication||
10卷2期（2005 / 06 / 30）
82 - 85
目的 探討人血白蛋白免疫誘導型及四氯化碳(CCl4)毒素誘導型所致大鼠肝纖維化模型肝組織中金屬蛋白酶組織抑制因子(TIMP)定位及表達狀態的差異。方法 分別以20%人血白蛋白進行免疫攻擊和CCl4。毒素攻擊大鼠，造模結束後對大鼠肝組織進行H-E、V-G染色及電鏡觀察；同時研究TIMP-1、TIMP-2蛋白及mRNA定位及表達狀態。結果 造模結束後，免疫誘導型模型肝組織病理改變具有進行性加重趨勢，TIMP-1、TIMP-2 mRNA及蛋白表達強度高、持續時間長；而毒素誘導型模型具有TIMP-1、TIMP-2 mRNA及蛋白表達強度弱、肝纖維化持續時間短等特點。免疫誘導實驗組肝臟中TIMP-1、TIMP-2相關抗原表達在肌成纖維細胞、成纖維細胞，以彙管區及纖維間隔中最明顯，陽性信號位於細胞胞質中，未見細胞核表達。原位雜交檢測結果亦相似。結論 毒素誘導型肝纖維化模型自然吸收較快，不利於抗肝纖維化藥物療效的觀察；免疫誘導型肝纖維化模型自然吸收時間較慢，且在造模結束後1~3個月有逐漸加重趨勢，有利於抗肝纖維化藥物療效觀察及肝纖維化機制研究。
Objective To investigate the difference of the location and expression of TIMP-1, 2 liver fibrosis model in rats between immune induced and toxin induced. Methods Immune rats were injected with 20% human serum albumin and intoxic rats with CCl4 respectively, then liver tissue of rats stained with HE, VG and observed with electron microscope. The location and expression of TIMP-1, TIMP-2 protein and mRNA were studied. Results Immune induced rat liver fibrosis model presented a tendency progressive aggrevation, strong expression of TIMP-1, TIMP-2 mRNA and protein and lasted for longer time, on the other hand, the toxin induced rat liver fibrosis model presented weak expression of TIMP-1, TIMP-2 mRNA and protein, and shorter period of liver fibrosis after stopping toxin attack. The TIMP-1, TIMP-2 related antigens in liver of immune induced model were expressed in myofibroblast and fibroblast. This was most obvious in portal area and fibrous septum. The positive signal located at cytoplasm, not in nucleus. Such distribution and location were also revealed in the in situ hybridization. Conclusion The toxin induced rat liver fibrosis model was not appropriate for observation of anti-fibrotic drugs due to its fast sponteneous absorption, the immune induced rat liver fibrosis model is good for the observation of anti-fibrotic drug effects and study on the mechanism of liver fibrosis due to its slow sponteneous absorption, and has the trend of aggrevation within three months after.