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[研究溶酶体相关膜蛋白2A在原发性胆汁性胆管炎免疫介导的肝损伤中的作用]

[Study the role of lysosome-associated membrane protein type 2A for immune-mediated liver injury of primary biliary cholangitis].

作者信息

Wang L, Zhang M, Sun K S, Zhou X, Han Y

机构信息

Department of Digestive Disease, Xijing Hospital, the Military Medical University of Air Force PLA, Xi'an 710032, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2018 Nov 20;26(11):847-851. doi: 10.3760/cma.j.issn.1007-3418.2018.11.008.

DOI:10.3760/cma.j.issn.1007-3418.2018.11.008
PMID:30616320
Abstract

To investigate the role of lysosome-associated membrane protein type 2A (LAMP-2A) for immune-mediated liver injury of primary biliary cholangitis (PBC). The association between LAMP-2A expression and PBC was examined by immunohistochemistry and electron microscopy in liver tissue samples from patients with PBC. Furthermore, the immunological damage of LAMP-2A overexpression on mouse liver was observed by adeno-associated virus (AAV) overexpression technique. The expression level of mRNA was analyzed by Student's t-test. The data were graphed and analyzed statistically using graphpad prism 5 (GraphPad Software).A value of p < 0.05 was considered statistically significant. The expression of LAMP-2A in liver tissue of PBC patients was increased, and the autophagosome formation was observed in hepatocytes. C57BL/6 mice were injected into the caudal vein with LAMP-2A AAV for 6 weeks. The formation of autophagosomes in mouse hepatocytes was increased significantly. The expression of related molecules was abnormal; simultaneously, the degree of lymphocyte infiltration in the liver tissue of mice was significantly higher than the control group. An overexpression of LAMP-2A in the liver of patients with PBC may induce and/or promote the hepatic inflammatory response, especially the portal inflammatory infiltrate.

摘要

研究溶酶体相关膜蛋白2A(LAMP-2A)在原发性胆汁性胆管炎(PBC)免疫介导的肝损伤中的作用。通过免疫组织化学和电子显微镜检查PBC患者肝组织样本中LAMP-2A表达与PBC之间的关联。此外,通过腺相关病毒(AAV)过表达技术观察LAMP-2A过表达对小鼠肝脏的免疫损伤。采用Student's t检验分析mRNA表达水平。使用GraphPad Prism 5(GraphPad软件)对数据进行绘图和统计分析。p < 0.05的值被认为具有统计学意义。PBC患者肝组织中LAMP-2A表达增加,且在肝细胞中观察到自噬体形成。将LAMP-2A AAV经尾静脉注射到C57BL/6小鼠体内6周。小鼠肝细胞中自噬体的形成显著增加。相关分子表达异常;同时,小鼠肝组织中淋巴细胞浸润程度明显高于对照组。PBC患者肝脏中LAMP-2A的过表达可能诱导和/或促进肝脏炎症反应,尤其是门脉炎症浸润。

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