原发性胆汁性胆管炎肝内胆管上皮细胞TLR4及上皮-间质转化相关标志物的表达

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目的：探讨原发性胆汁性胆管炎（PBC）肝内胆管上皮细胞（IBEC）TLR4和上皮-间质转化（EMT）标志物的表达及二者的相关性。方法：应用免疫组织化学技术检测上海长征医院就诊的11例PBC患者和5例正常对照者（肝移植供肝者）的肝组织IBEC中TLR4和EMT相关标志物[E-钙黏蛋白和波形蛋白（Vimentin）]的阳性表达率，分析TLR4与EMT的关系及与PBC纤维化进展的相关性。结果：TLR4在正常对照组IBEC中无表达，在PBC组IBEC表达明显，各期患者TLR4阳性率分别为I期28.6%、II期41.6%、III期64.0%、IV期73.1%，除I期与II期及III期与IV期之间外，各组间差异均有统计学意义（P＜0.01）；E-钙黏蛋白在正常对照组IBEC中有表达，在PBC组IBEC中表达明显降低，各期E-钙黏蛋白阳性率分别为I期84.0%、II期48.1%、III期23.0%、IV期19.0%，除正常对照组与I期及III期与IV期外各组间差异均有统计学意义（P＜0.01）；Vimentin在正常对照组IBEC中无表达，在PBC组IBEC中表达升高，各期Vimentin阳性率分别为I期30.0%、II期40.1%、III
期73.7%、IV期77.0%，除I期与II期以及III期与IV期外，各组间差异均有统计学意义（P＜0.01）；PBC患者IBEC TLR4表达与E-钙黏蛋白呈显著负相关（r=-0.927，P＜0.001），与Vimentin呈显著正相关（r=0.918，P＜0.001），E-钙黏蛋白表达与Vimentin呈显著负相关（r=-0.918，P＜0.001）。结论：PBC中IBEC TLR4表达明显增高，存在明显EMT现象，TLR4与EMT密切相关，且与PBC纤维化进展关系密切。

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	刘东红
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	梁艳

关键词 ： Toll样受体4, 上皮-间质转化, 原发性胆汁性胆管炎, 免疫组织化学

Abstract：Objective: To explore the expression levels of Toll-like receptor 4 (TLR4) and epithelial-mesenchymal transition (EMT)-related markers in intrahepatic biliary epithelial cells (IBEC) and their association in patients with primary biliary cholangitis (PBC). Methods: Immunohistochemistry assay was used to detect the expression levels of TLR4 and EMT-related markers (E-cadherin and vimentin) in IBEC from liver tissues of 11 PBC patients and 5 healthy controls (donors for liver transplantation) from Shanghai Changzheng Hospital. The correlations between TLR4, EMT and PBC fibrosis progression were analyzed. Results: No expression of TLR4 was observed in IBEC of healthy individuals, while significant expression was found in PBC patients. The positive ratios of TLR4 in PBC patients were 28.6%, 41.6%, 64.0% and 73.1% in stage 1, 2, 3 and 4, respectively. The differences were statistically significant between stages except for stage 1 vs. 2 and stage 3 vs. 4 (P<0.01). The expression level of E-cadherin was significantly decreased in IBEC of PBC patients, compared with that of healthy individuals. The positive ratios of E-cadherin were 84.0%, 8.1%, 23.0% and 19.0% respectively in stage 1, 2, 3 and 4 in PBC patients. The differences were statistically significant between groups except for healthy group vs. stage 1 and stage 3 vs. 4 (P<0.01). There was no expression of vimentin in IBEC of healthy individuals, while significant expression in PBC patients. The positive ratios of vimentin were 30.0%, 40.1%, 73.7% and 77.0%, respectively in stage 1, 2, 3 and 4 in PBC patients. There were statistically significant differences between stages except stage 1 vs. 2 and stage 3 vs. 4 (P<0.01). The positive ratio of TLR4 in IBEC had significant negative correlation with that of E-cadherin (r=-0.927, P<0.001), but positively related to that of vimentin (r=0.918, P<0.001). Additionally, the positive ratio of E-cadherin had also significant negative association with that of vimentin (r= -0.918, P<0.001). Conclusion: The expression of TLR4 is increased and EMT occurs in IBEC of PBC patients. Furthermore, TLR4 is closely associated with EMT and both of them show close correlation with PBC fibrosis progression.

Key words： Toll-like receptor 4 epithelial-mesenchymal transition primary biliary cholangitis immuno-histochemistry

基金资助:国家自然科学基金资助项目（81001333，81571591，81671594）。

作者简介: 刘东红（1978-），男，江西赣州人，副主任技师。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I8/567

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