| 李春霞,李晨语,于文沛,马群,熊化保.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[J].济宁医学院学报,2022,45(5):328-334 |
| 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 |
| 投稿时间：2022-09-13 |
| DOI：10.3969/j.issn.1000-9760.2022.05.005 |
| 中文关键词: 白细胞介素16;Con A;免疫性肝损伤;髓源性抑制细胞 |
| 英文关键词: Interleukin-16;Con A;Immune liver injury;Myeloid-derived suppressor cells (MDSCs) |
| 基金项目: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) |
| 作者 | 单位 | E-mail | | 李春霞 | 济宁医学院免疫学与分子医学研究所, 济宁 272067 | | | 李晨语 | 济宁医学院免疫学与分子医学研究所, 济宁 272067 | | | 于文沛 | 济宁医学院免疫学与分子医学研究所, 济宁 272067 | | | 马群 | 济宁医学院免疫学与分子医学研究所, 济宁 272067 | | | 熊化保 | 济宁医学院免疫学与分子医学研究所, 济宁 272067 | xionghbl@yahoo.com |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| Objective To investigate the effect of IL-16 in the development of Con A-induced autoimmune liver injury and explore its mechanism.Methods C57BL/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 Arespectively.Con A groups were injected with Con Aby 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.Afterliver injury mold created by IL-16-/-mice,the survival rate of the mice was observed,the levels of transaminases and inflammatory factors in serum were tested,the pathology of liver tissue 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 ofiNOS and Arg-1was tested by qPCR.Results The expression of IL-16 was increased in serum and liver tissue of Con A-induced autoimmune 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-α 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 expression of iNOS fromIL-16-/--mice were increased.Conclusion IL-16 aggravates Con A-induced liver injury by downregulatingthe accumulation of MDSCs. |
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