胆道闭锁为发生于婴儿时期严重影响儿童生长发育的疾病，目前病因及发病机制仍未明确，国际上大部分研究结果显示胆道闭锁为遗传因素与环境因素综合致病。本研究针对GPC1基因进行研究，应用RealTime-RT-PCR及WesternBlot方法探索该基因在胆道闭锁患儿中表达变化；应用PCR及基因测序技术探索该基因在胆道闭锁患儿中的突变情况；应用RealTime-RT-PCR、WesternBlot及原位荧光免疫组化染色方法探索该基因及肝纤维化相关基因（HSP47，VIME，FGF）表达的相关性，最终明确GPC1在胆道发病中的遗传易感性作用及其对胆道闭锁肝脏纤维化的影响，为胆道闭锁发病机制及其肝纤维化相关理论及临床研究提供思路，为相关干预措施的研究提供方向。 

Biliary atresia is a severe infantile disease which affects growth and development badly. The etiology and pathogenesis of this disease remain unclear, but it seems to be caused by the combination of genetic and environmental factors according to most articles published globally. This study will focus on GPC1 gene, search for its expression changes in biliary atresia using RealTime-RT-PCR and WesternBlot technology, seek for its mutation in biliary atresia using gene sequencing technology, and discuss its expression relativity with liver fibrosis relavant gene(HSP47,VIME,FGF) using RealTime-RT-PCR, Westernblot and in situ immunofluorescence histochemical staining technology, and eventually find out the genetic susceptibility of GPC1 in biliary atresia and its impact on liver fibrosis, which may shed light on the research of pathogenesis and liver fibrosis in biliary atresia theoreticlly and clinically, and provide research direction for intervention measures.

本研究GPC1在BA患儿及罹患其他肝脏疾病儿童中表达及基因序列的差异进行了对比研究，得出两者存在显著的统计学差异，即GPC1基因在胆道闭锁中为显著低表达，证实了在中国人群胆道闭锁患儿中GPC1基因可能为遗传易感基因。通过对胆道闭锁及对照组的患儿的肝脏组织纤维化程度及临床表现进行统计分析，提出了GPC1基因可能参与的机制是通过影响胆道发育的水平。