摘要： 目的 探讨控制小鼠单核增生性李斯特菌易感性的遗传位点Listr1对非酒精性脂肪性肝病（NAFLD）易感性的影响及其初步机制。方法 利用BALB/c背景的携带C56BL/6来源Listr1等位基因的C.B6By-Listr1同类系小鼠和BALB/c小鼠，通过高脂高糖饮食建立NAFLD模型。在第4、8、12、16和20周检测比较2种小鼠肝脏病理、细胞因子表达水平和肝内巨噬细胞活化。结果 C.B6By-Listr1小鼠体质量和肝脂肪变性程度明显低于野生型BALB/c小鼠；12周后C.B6By-Listr1小鼠肝内白细胞介素-1β、单核细胞趋化蛋白-1、肿瘤坏死因子-α表达水平低于BALB/c小鼠；第16和20周，C.B6By-Listr1小鼠肝纤维化和巨噬细胞活化较野生型小鼠轻。结论 Listr1遗传位点影响小鼠对NAFLD的易感性，可能与其影响肝内巨噬细胞的活化和功能有关。

Listr1遗传位点对小鼠非酒精性脂肪性肝病易感性的影响

吴灵霞, 韩雪, 高康宁, 祁赞梅

中国医科大学基础医学院免疫学教研室, 沈阳 110122

收稿日期:2020-09-24出版日期:2021-09-30发布日期:2021-09-18
通讯作者:祁赞梅E-mail:zmqi@cmu.edu.cn
作者简介:吴灵霞(1996-),女,硕士研究生.
基金资助:辽宁省自然科学基金（20180550513）


关键词: Listr1遗传位点, 非酒精性脂肪性肝病, 巨噬细胞
Abstract: Objective To determine the influence of the Listr1 gene locus,which controls the susceptibility of mice to Listeria monocytogenes,on murine susceptibility to non-alcoholic fatty liver disease (NAFLD) and to elucidate the primary mechanism involved. Methods An NAFLD model was established in C.B6By-Listr1 mice bearing the C57BL/6-derived Listr1 allele on a BALB/c background and in wild-type (WT) BALB/c mice through feeding of a high-fat and high-fructose diet to the animals. At weeks 4,8,12,16,and 20,two mice from each group were selected for the analysis and comparison of their liver pathology,cytokine expression levels,and macrophage activation in the liver. Results Generally,the C.B6By-Listr1 mice had lower body weights and steatosis than the WT mice. The interleukin-1beta,monocyte chemotactic protein-1,and tumor necrosis factor-alpha expression levels were lower in the C.B6by-Listr1 mice than in the WT mice after 12 weeks. At weeks 16 and 20,hepatic fibrosis and macrophage activation were significantly attenuated in the C.B6By-Listr1 mice compared with that in the WT mice. Conclusion The Listr1 gene locus controls the susceptibility of mice to NAFLD by influencing the activation and function of hepatic macrophages.
Key words: Listr1 genetic loci, non-alcoholic fatty liver disease, macrophage
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