低氧诱导因子-1α对胶原诱导关节炎小鼠脾细胞中T细胞亚群的调控作用  

Regulation of hypoxia inducible factor-1αon T cell subsets in splenocytes with collagen induced arthritis mice

作　　者：孟金 康敏 芦彦蓉 郭煜 庞春艳[1] MENG Jin;KANG Min;LU Yanrong;GUO Yu;PANG Chunyan(Central laboratory,The First Affiliated Hospital of Baotou Medical College(Inner Mongolia Key Laboratory of Autoimmunity),Baotou 014010,China;Baotou Medical College)

机构地区：[1]包头医学院第一附属医院中心实验室(内蒙古自治区自体免疫学重点实验室),内蒙古包头014010 [2]包头医学院

出　　处：《包头医学院学报》2023年第5期17-21,28,共6页Journal of Baotou Medical College

基　　金：内蒙古自治区自然科学基金资助项目(2019LH08043)。

摘　　要：目的:探讨低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)的小干扰RNA(small interfering RNA,siRNA)载体对胶原诱导关节炎(collagen induced arthritis,CIA)小鼠脾细胞中T细胞亚群的调控作用。方法:DBA/1小鼠采用牛Ⅱ型胶原建立类风湿关节炎的动物模型CIA小鼠,尾静脉注射HIF-1α-siRNA腺病毒和阴性对照腺病毒,每周1次,共4周,实验分为空白组、模型组、阴性对照组和HIF-1α-siRNA组。实验结束后处死小鼠。流式细胞术检测小鼠脾脏中Th1和Th2、Th17和Treg比例的变化;HE染色观察小鼠踝关节的病理变化。结果:与空白组比较,模型组小鼠脾细胞中Th1细胞和Th17细胞的比例升高,差异有统计学意义(P<0.05);Treg的比例是下降的,但没有明显的统计学差异;而Th2细胞的变化并不明显。与模型组和阴性对照组比较,HIF-1α-siRNA组小鼠脾细胞中Th1细胞和Th17细胞的比例降低,差异有统计学意义(P<0.05),Th2细胞和Treg虽然呈上升的趋势,但差异没有统计学意义;模型组小鼠踝关节出现滑膜增生及大量的淋巴细胞浸润,HIF-1α-siRNA作用后,CIA小鼠踝关节的滑膜增生和淋巴细胞浸润的情况明显减轻。结论:HIF-1α-siRNA可以降低脾细胞中Th1细胞和Th17细胞的比例,同时上调Th2细胞和Treg的比例,并减轻CIA小鼠滑膜增生和淋巴细胞浸润情况,提示HIF-1α-siRNA可以通过调控脾细胞中的T细胞亚群,进而发挥治疗CIA小鼠的作用。Objective:To investigate the regulation of hypoxia inducible factor-1α(HIF-1α)on T lymphocyte subsets in splenocytes with collagen induced arthritis(CIA)mice by small interfering RNA(siRNA)vector.Methods:the animal model of rheumatoid arthritis was established in DBA/1 mice were injected by bovine typeⅡcollagen.CIA mice were injected with HIF-1α-siRNA adenovirus and negative control adenovirus,once a week for 4 weeks.The experiment was divided into control group,model group,negative control group and HIF-1α-siRNA group.The mice were killed after the experiment.The proportion of Th1cells and Th2 cells,Th17 cells and Tregs in mice spleen were detected by flow cytometry,the pathological changes of mouse ankle was observed by HE staining.Results:Compared with control group,the proportion of Th1 cells and Th17 cells in splenocytes of model group increased,the difference was statistically significant(P<0.05),the proportion of Tregs decreased,but there was no significant statistical difference,while the change of Th2 cells was not obvious.Compared with model group and negative control group,the proportion of Th1 cells and Th17 cells in splenocytes of mice in HIF-1α-siRNA group decreased,and the difference was statistically significant(P<0.05),Although Th2 cells and Tregs showed an upward trend,the difference was not statistically significant.In model group,synovial hyperplasia and a large number of lymphocytes infiltrated in the ankle joint,after HIF-1α-siRNA treated CIA mice,synovial hyperplasia and the lymphocyte infiltration of mice ankle joint was significantly reduced.Conclusion:The proportion of Th1 cells and Th17 cells in the spleen of mice were reduced,the proportion of Th2 cells and Tregs in the spleen of mice were increased,synovial hyperplasia and lymphocytes infiltration were relieved.HIF-1α-siRNA play a role in the treatment of CIA mice by regulating T cell subsets in splenocytes.

关 键 词：胶原诱导关节炎 低氧诱导因子-1Α Th17细胞 TREG TH1细胞 TH2细胞 

分 类 号：R593.22[医药卫生—内科学]