IL-16在Con A诱导小鼠自身免疫性肝损伤发生发展中的作用  

The role of IL-16 in the development of Con A-induced autoimmune liver injury in mice

作　　者：李春霞[1] 李晨语 于文沛 马群[1] 熊化保[1] LI Chunxia;LI Chenyu;YU Wenpei;MA Qun;XIONG Huabao(Immunology and Molecular Medicine Institute,Jining Medical University,Jining 272067,China)

机构地区：[1]济宁医学院免疫学与分子医学研究所,济宁272067

出　　处：《济宁医学院学报》2022年第5期328-334,共7页Journal of Jining Medical University

基　　金：山东省自然科学基金(ZR2020MH163);山东省医药卫生科技发展计划项目(2019WS356);济宁医学院大学生创新训练计划项目(cx2022071z)。

摘　　要：目的 探讨IL-16在Con A诱导的小鼠自身免疫性肝损伤发生发展中的作用及其机制。方法 将C57BL/6小鼠(WT)及IL-16敲除(IL-16^(-/-))小鼠分别随机分为WT-control组、IL-16^(-/-)-control组、WT-Con A组和IL-16^(-/-)-Con A组。Con A组给予尾静脉注射刀豆球蛋白A(concanavalin A,Con A),建立自身免疫性肝损伤模型,control组尾静脉注射相同体积的磷酸缓冲盐溶液(PBS)。ELISA、实时定量PCR及免疫组化检测各组血清及肝组织IL-16的表达;IL-16^(-/-)小鼠造模后,观察肝损伤小鼠的生存率,检测血清中转氨酶及炎性因子的水平,HE染色及TUNEL分析肝组织病理,流式细胞术检测肝、脾组织中髓源性抑制细胞(MDSCs)的比例。取WT小鼠(WT组)及IL-16^(-/-)小鼠(IL-16^(-/-)组)股骨及胫骨,体外诱导MDSCs,流式细胞术分析MDSCs比例,实时定量PCR检测MDSCs免疫抑制相关因子诱导型一氧化氮合酶(iNOS)、精氨酸酶1(Arg-1)的mRNA水平。结果 与WT-control组相比,WT-Con A组小鼠血清及肝组织中IL-16表达明显增加(均P<0.001)。与WT-Con A组相比,IL-16^(-/-)-Con A组小鼠生存率明显提高(P<0.05);血清中ALT、AST及IL-6、IL-12、TNF-α炎性因子的水平明显降低(均P<0.05);肝组织损伤减轻,肝细胞凋亡减少;肝、脾组织中MDSCs的募集增加(均P<0.05)。体外实验发现,与WT组相比,IL-16^(-/-)组来源诱导的MDSCs比例及iNOS的表达明显增加(均P<0.05)。结论 IL-16可通过下调MDSCs的募集加重Con A诱导的肝损伤。Objective To investigate the effect of IL-16 in the development of Con A-induced autoimmune liver injury and explore its mechanism.MethodsC57BL/6 mice(WT)and IL-16 knockout(IL-16)mice were randomly divided into four groups:WT-control,IL-16/-control,WT-Con A,and IL-16/-Con A respec-tively.Con A groups were injected with Con A by the tail vein,and the control groupswere injected with the same volume of PBS.ELISA,real-time quantitative PCR,and immunohistochemistry were used to detect the expression of IL-16.After liver injury mold created by IL-16/mice,the survival rate of the mice was ob-served,the levels of transaminases and inflammatory factors in serum were tested,the pathology of liver tis-sue was analyzed by HE staining and TUNEL,and the proportion of MDSCs in liver and spleen was detected by flow cytometry.The femur and tibia of WT mice and IL-16-/-mice were taken to induce MDSCs in vitro.The proportion of MDSCs was analyzed by flow cytometry.The level mRNA of iNOS and Arg-lwas tested by qPCR.Results The expression of IL-16 was increased in serum and liver tissue of Con A-induced autoim-mune liver injury mice.Knockdown of IL-16 can improve the survival rate of mice,reduce the levels of ALT,AST,IL-6,IL-12,and TNF-a in serum,improve liver tissue damage,reduce liver cell apoptosis,and increase the accumulation of MDSCs in liver and spleen.In vitro experiments shows,the ratio of MDSCs and the ex-pression of iNOS from IL-16/-mice were increased.ConclusionL-16 aggravates Con A-induced liver injury by downregulating the accumulation of MDSCs.

关 键 词：白细胞介素16 Con A 免疫性肝损伤 髓源性抑制细胞 

分 类 号：R392[医药卫生—免疫学]