毒素型及免疫型大鼠纤维化肝组织中金属蛋白酶组织抑制因子定位及表达差异  

Comparison of the location and expression of TIMPs between immune induced and toxin induced liver fibrosis model in rat

作　　者：聂青和[1] 谢玉梅[1] 周永兴[1] 罗新栋[1] 罗红[1] 程勇前[1] 

机构地区：[1]第四军医大学唐都医院全军感染病诊疗中心,西安710038

出　　处：《肝脏》2005年第2期82-85,共4页Chinese Hepatology

基　　金：中国博士后科学基金资助项目(中博基[1999]10号);陕西省科技攻关项目(2003K10G63)

摘　　要：目的探讨人血白蛋白免疫诱导型及四氯化碳(CCl4)毒素诱导型所致大鼠肝纤维化模型肝组织中金属蛋白酶组织抑制因子(TIMP)定位及表达状态的差异。方法分别以20%人血白蛋白进行免疫攻击和CCl4毒素攻击大鼠,造模结束后对大鼠肝组织进行HE、VG染色及电镜观察;同时研究TIMP1、TIMP2蛋白及mRNA定位及表达状态。结果造模结束后,免疫诱导型模型肝组织病理改变具有进行性加重趋势,TIMP1、TIMP2mRNA及蛋白表达强度高、持续时间长;而毒素诱导型模型具有TIMP1、TIMP2mRNA及蛋白表达强度弱、肝纤维化持续时间短等特点。免疫诱导实验组肝脏中TIMP1、TIMP2相关抗原表达在肌成纤维细胞、成纤维细胞,以汇管区及纤维间隔中最明显,阳性信号位于细胞胞质中,未见细胞核表达。原位杂交检测结果亦相似。结论毒素诱导型肝纤维化模型自然吸收较快,不利于抗肝纤维化药物疗效的观察;免疫诱导型肝纤维化模型自然吸收时间较慢,且在造模结束后1～3个月有逐渐加重趋势,有利于抗肝纤维化药物疗效观察及肝纤维化机制研究。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 CCL 4 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.

关 键 词：毒素型 免疫型 大鼠 肝纤维化 肝组织 金属蛋白酶组织抑制因子 基因定位 基因表达 四氯化碳 

分 类 号：R575.2[医药卫生—消化系统]