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目的:探索表皮生长因子(epidermal growth factor,EGF)对胆管上皮细胞增殖和上皮间充质转化(epithelial mesenchymal transition,EMT)的作用,为胆道闭锁(biliary atresia, BA)肝纤维化的发生机制和治疗方向提供实验依据。方法:收集2019年1月至2020年1月就诊的28例BA和9例胆总管囊肿患儿的肝组织样本,分别作为BA肝脏组和对照肝脏组;收集28例中20例BA患儿的血清,并收集5例胆汁淤积患儿和20例年龄匹配健康体检婴幼儿的血清,分别作为BA血清组、疾病对照血清组和正常对照血清组。通过CK19和N-cadherin免疫组织化学检测肝组织胆管增生和EMT情况;通过酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测血清EGF的表达水平;进行体外人肝内胆管上皮细胞系(human intrahepatic biliary epithelial cell,HIBEpiC)培养,检测经EGF干预后细胞增殖和EMT的变化。结果:较对照肝脏组,BA肝脏组中胆管增生显著,差异具有统计学意义(n P<0. 001),胆管增生程度与肝纤维化程度正相关,增生的小胆管可分泌大量间质细胞成分。BA血清组EGF表达水平显著高于正常对照血清组,差异具有统计学意义(n P<0. 001),BA肝脏组EGF mRNA水平显著高于对照肝脏组,差异具有统计学意义(n P<0. 001),血清和肝组织EGF水平与肝纤维化程度相关。EGF可明显促进体外胆管上皮细胞增殖,EGF可诱导体外胆管上皮细胞发生EMT。n 结论:EGF在BA中高表达,是促进肝内胆管上皮细胞增殖与EMT的重要诱导因子,其在BA肝纤维化进程中起重要作用。“,”Objective:To explore the effect of epidermal growth factor (EGF) on the proliferation of biliary epithelial cells and epithelial mesenchymal transition (EMT) and provide experimental rationales for the mechanisms and therapeutics of liver fibrosis in biliary atresia (BA).Methods:From January 2019 to January 2020, liver tissue samples were collected from 28 BA children and 9 children with choledochal cyst as BA liver control group. Serum samples were collected from 28 BA children, 5 children with cholestasis and 20 age-matched healthy infants. Serum of BA patients, disease control serum and normal control serum groups were designated. Bile duct proliferation and EMT in liver tissue were detected by CK19 and N-cadherin immunohistochemistry ; the seral expression level of EGF was detected by enzyme-linked immunosorbent assay (ELISA) ; human biliary intraepithelial cell (HIBEpiC) culture was performed in vitro for detecting the changes of cell proliferation and EMT after EGF intervention.Results:As compared with control liver group, bile duct proliferation of BA liver was significant and the difference was statistically significant (n P<0. 001). The degree of bile duct proliferation was positively correlated with degree of liver fibrosis and hyperplastic small bile ducts secreted a large number of interstitial cell components. EGF expression level was significantly higher in BA serum group than that in normal control serum group (n P<0. 001). EGF mRNA level was significantly higher in BA liver group than that in control liver group (n P<0. 001). And EGF levels in sera and liver tissues were correlated with the degree of liver fibrosis. EGF could significantly promote the proliferation of biliary epithelial cells in vitro and EGF induced EMT in biliary epithelial cells in vitro.n Conclusions:Highly expressed in BA, EGF is an important inducer of promoting the proliferation and EMT of biliary epithelial cells. And it plays an important role in the process of liver fibrosis in BA.