摘要
目的:探讨miR-150缺失对链脲佐菌素(STZ)诱导小鼠Ⅰ型糖尿病(T1DM)发生的影响及其免疫学机制。方法:将小鼠分为miR-150基因敲除组(150KO)及其野生型正常对照,利用STZ体内注射诱导T1DM。ELISA检测糖尿病相关自身抗体变化;流式细胞术检测小鼠脾脏CD4+T细胞、CD8+T细胞、B细胞以及调节性T细胞(Treg)比率变化,采用细胞内染色检测CD4+T细胞IFN-γ、IL-4和IL-17表达变化。结果:miR-150缺失可显著加速STZ诱导的小鼠T1DM发生。与WT小鼠相比,150KO小鼠血清糖尿病相关自身抗体水平显著升高,但STZ处理只显著提高了WT小鼠糖尿病相关自身抗体水平,对150KO小鼠抗体水平没有影响。与STZ处理的WT小鼠相比,STZ处理的150KO小鼠脾脏CD4+T细胞、CD8+T细胞和B细胞比率差异无统计学意义,但Treg比率显著降低。STZ处理的150KO小鼠CD4+T细胞中IFN-γ和IL-17表达阳性率与WT小鼠相比显著提高,但IL-4表达阳性率变化无统计学意义。结论:miR-150缺失不影响STZ处理小鼠糖尿病相关自身抗体变化,但会导致Treg减少,CD4+T细胞中IFN-γ和IL-17表达上升,说明miR-150缺失主要通过细胞免疫应答加速小鼠T1DM发生。
Objective:To investigate effect of miR-150 deletion on occurrence of type I diabetes mellitus(T1DM)in mice and its immunological mechanism.Methods:Mice were divided into miR-150 knockout(150KO)and wild-type normal control group(WT),and T1DM was induced by streptozotocin(STZ)injected.Changes in serum diabetes-related autoantibodies were detected by ELISA,and changes in ratios of CD4+T cells,CD8+T cells,B cells and regulatory T cells(Treg)in the spleen of mice were detected by flow cytometry.Expressions of IFN-γ,IL-4 and IL-17 in CD4+T cells were detected by intracellular staining.Results:miR-150 deletion significantly accelerated the occurrence of STZ-induced T1DM in mice.Compared with WT mice,serum level of diabetic autoantibodies in 150KO mice were significantly increased,while STZ treatment only significantly increased level of autoantibodies in WT mice,but had no effect on level of antibodies in 150KO mice.Compared with WT mice treated with STZ,ratio of CD4+T cells,CD8+T cells and B cells in spleen of 150KO mice treated with STZ were not significantly change,but ratio of Treg was significantly reduced.Positive expression rates of IFN-γand IL-17 in CD4+T cells of 150KO mice treated with STZ were significantly increased compared with WT mice,but positive rates of IL-4 were not significantly changed.Conclusion:miR-150 deletion did not affect changes of diabetic autoantibodies in STZ-treated mice,but it led to decreased Treg and increased expressions of IFN-γand IL-17 in CD4+T cells,indicating that miR-150 deletion mainly accelerated the occurrence of T1DM in mice through cellular immune response.
作者
高丽清
梁靖
张爽
李钰锐
李洁心
刘潇
刘美丽
段一硕
赵亚林
张琦
李晓晓
张冰
王勇满
李秋飞
郑全辉(指导)
GAO Li-Qing;LIANG Jing;ZHANG Shuang;LI Yu-Rui;LI Jie-Xin;LIU Xiao;LIU Mei-Li;DUAN Yi-Shuo;ZHAO Ya-Lin;ZHANG Qi;LI Xiao-Xiao;ZHANG Bing;WANG Yong-Man;LI Qiu-Fei;ZHENG Quan-Hui(School of Basic Medical Sciences,North China University of Science and Technology,Hebei Key Laboratory for Chronic Diseases,Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases,Tangshan 063210,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2020年第22期2693-2696,2701,共5页
Chinese Journal of Immunology
基金
国家自然科学基金面上项目(81373111,81673208)
河北省卫生和计划生育委员会科研基金项目(20190105)资助。
