中文摘要
胆道闭锁是新生儿和婴儿阻塞性黄胆常见的原因之一,Kasai术是目前最主要的治疗手段,但术后肝纤维化进程难以阻止,最终导致肝硬化,如何减缓、逆转肝纤维化进程是改善本病预后的关键。TGF-β1/smads通道在肝星状细胞的激活、细胞外基质的生成、肝纤维化进程中起着重要作用,而MMPs/TIMPs是机体内调节和清除过多细胞外基质的重要系统,阻断此通道的信号传导及调节细胞外基质的沉积可有效延缓肝纤维化的发生。本课题在既往研究基础上,通过建立胆道闭锁小鼠模型进行在体及离体实验:采用Western Blotting检测肝组织TGF-β1、Tβ1R、Smad3/7、MMPs/TIMPs,RT-PCR检测Tβ1R及Smad3/7 mRNA,原位杂交法检测肝组织MMPs/TIMPs mRNA并作图像分析,ELISA法检测胶原蛋白量的变化,研究加味茵陈四逆汤治疗本病的作用机制及靶点,为临床应用提供依据。
英文摘要
Biliary atresia is one of the common causes of neonatal obstructive jaundice,At present,operation of Kasai is the main treatment .But it is difficult to prevent progressive liver fibrosis,and eventually lead to cirrhosis,how to slow down and reverse the process of liver fibrosis is the key point which can improve the prognosis. TGF-β1/smads channel plays an important role in activing the hepatic stellate cells and generating extracellular matrix in the process of liver fibrosis; Moreover,MMPs / TIMPs is an important system of regulating and removing excessive extracellular matrix in the body.Blocking signal transduction and adjusting the deposition of extracellular matrix of the channel can effectively delay the occurrence of liver fibrosis. On the basis of our previous studies. we will do experiments which include in vitro and in vivo by establishing Biliary atresia mice model : detecting TGF-β1、 Tβ1R、Smad3 / 7 、MMPs / TIMPs of liver tissue by Western Blotting ;detecting mRNA of Tβ1R、 Smad3/7 by RT-PCR;detecting MMPs/TIMPs mRNA of liver tissue In situ hybridization and making analysis of Image .Analysis; detecting the change in the amount of collagen by ELISA; revealing the mechanism and working target of Chinese medicine which can provid theoretical basis for clinical application.
