泡球蚴感染中自噬相关蛋白对巨噬细胞极化的影响  

Effect of autophagy-related proteins on macrophage polarization in Echinococcus multilocularis infection

作　　者：蔡璇琳 李斌[1,3] 古力米热·买买提吐尔逊 周璇 吕洁 麦迪乃姆·艾比布拉 赵慧[1,3] 单骄宇 齐新伟 马秀敏[1,2,3] CAI Xuan-lin;LI Bin;GULIMIRE Maimaitituerxun;ZHOU Xuan;LV Jie;Maidinaimu Aibibula;ZHAO Hui;SHAN Jiao-yu;QI Xin-wei;MA Xiu-min(Laboratory,Cancer Hospital Affiliated with Xinjiang Medical University,State Key Laboratory of Pathogenesis,Prevention,and Treatment of Diseases Highly Endemic to Central Asia,Urumqi,China 830011;College of Basic Medicine,Xinjiang Medical University;First Hospital Affiliated with Xinjiang Medical University)

机构地区：[1]新疆医科大学附属肿瘤医院检验科,省部共建中亚高发病成因与防治国家重点实验室,新疆乌鲁木齐830011 [2]新疆医科大学基础医学院 [3]新疆医科大学第一附属医院

出　　处：《中国病原生物学杂志》2021年第6期634-638,共5页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.82060372,81760372);新疆科技厅项目(No.2020E0277);自治区大学生创新项目(No.S202010760002);省部共建中亚高发病成因与防治国家重点实验室项目(No.SKL-HIDCA-2020-YG3,SKL-HIDCA-2020-BC5)。

摘　　要：目的通过对感染泡球蚴小鼠肝脏的自噬相关蛋白以及巨噬细胞不同分型的检测,探讨在泡球蚴感染过程中自噬对巨噬细胞极化的影响及可能机制。方法取雌性BALB/c小鼠16只,随机分为实验组与对照组。实验组建立泡球蚴感染小鼠模型,于感染90天处死,通过HE染色观察小鼠肝脏的病理学变化,利用免疫组化等技术检测肝脏中自噬相关蛋白的表达,利用免疫荧光激光共聚焦法进行肝脏组织巨噬细胞与自噬相关蛋白共定位,采用流式细胞术检测肝脏巨噬细胞M1、M2表达水平。结果感染90天时,实验组小鼠肝脏自噬相关蛋白LC3、p62表达均增高,相对表达量分别为2.08±0.3和1.85±0.2,与对照组比较差异均有统计学意义(F值分别为260.114和434.116,均P<0.01);实验组小鼠肝脏组织中自噬相关蛋白LC3、p62与巨噬细胞存在共定位表达,Pearson’s相关系数与对照组比较有统计学意义(F值分别为132.219和36.325,均P<0.01),Manders重叠系数与对照组比较有统计学意义(F值分别为205.410和140.665,均P<0.01);实验组小鼠肝脏巨噬细胞数增加至31.74±1.68,M1型巨噬细胞增加至66.46±1.82,M2型巨噬细胞减少至22.46±0.63,与对照组比较差异均有统计学意义(F值分别为309.358、194.001和759.194,均P<0.01)。结论泡球蚴感染小鼠肝脏自噬相关蛋白高表达,促进巨噬细胞以M1型极化,抑制M2型极化,以减轻炎症反应,帮助机体清除病原体。Objective To detect autophagy-related proteins in the liver of mice infected with Echinococcus multilocularis and the different types of macrophages in order to investigate the effect of autophagy on the polarization of macrophages and its possible mechanism in the process of E.multilocularis infection.Methods Sixteen female BALB/c mice were randomly divided into experimental groups and control groups.The experimental group served as a mouse model of E.multilocularis infection and was sacrificed 90 d after infection.Pathological changes in the mouse liver were observed using HE staining,and the expression of autophagy-related proteins in the liver was detected immunohistochemically.Co-localization of liver tissue macrophages and autophagy-related proteins were determined using immunofluorescence and confocal laser scanning,and the levels of M1 and M2 expression in liver macrophages were detected using flow cytometry.Results At 90 days postinfection,the levels of expression of the autophagy-related proteins LC3 and p62 in the liver of mice in the experimental group increased,with relative levels of expression of 2.08±0.3 and 1.85±0.2.Both levels differed significantly compared to levels in the control group(F-values of 260.114 and 434.116,respectively;P<0.01 for all).The liver tissues of mice in the experimental group displayed co-located expression of the autophagy-related proteins LC3 and p62 and macrophages.Pearson’s correlation coefficient was significant compared to that in the control group(F-values of 132.219 and 36.325,respectively;P<0.01 for all),and Manders’overlap coefficient was significant compared to that in the control group(F-values of 205.410 and 140.665,respectively:P<0.01 for all).The number of liver macrophages in the experimental group increased to 31.74±1.68,M1-type macrophages increased to 66.46±1.82,and M2-type macrophages decreased to 22.46±0.63.Those numbers of macrophages all differed significantly compared to numbers in the control group(F-values of 309.358,194.001,and 759.194,

关 键 词：泡球蚴 自噬相关蛋白 巨噬细胞极化 

分 类 号：R383.33[医药卫生—医学寄生虫学]