PAD4-siRNA调控T细胞亚群缓解CIA小鼠的疾病进展  

PAD4-siRNA alleviates disease progression of collagen-induced arthritis mice by regulating T cells subpopulation

作　　者：芦彦蓉 赵凯 庞春艳[1] Lu Yanrong;Zhao Kai;Pang Chunyan(Central Laboratory,The First Affiliated Hospital of Baotou Medical College,Baotou 014010;Dept of Rheumatology,The First Affiliated Hospital of Baotou Medical College,Baotou 014010)

机构地区：[1]包头医学院第一附属医院中心实验室,包头014010 [2]包头医学院第一附属医院风湿免疫科,包头014010

出　　处：《安徽医科大学学报》2025年第2期272-278,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81560270)。

摘　　要：目的探讨肽基精氨酸脱亚氨酶4(PAD4)的小干扰RNA(siRNA)载体病毒和感染PAD4-siRNA病毒的小鼠脾细胞对胶原诱导关节炎(CIA)小鼠治疗效果和潜在作用机制。方法实验分对照组、模型组、治疗1组、治疗2组,每组7只小鼠。对照组小鼠不做任何处理,其余3组小鼠构建CIA模型,模型组小鼠注射磷酸盐缓冲液(PBS),治疗1组的小鼠注射PAD4-siRNA病毒载体;治疗2组的小鼠注射含有PAD4-siRNA病毒载体的小鼠脾细胞,每周1次,共8周。实验结束后处死小鼠,检测小鼠脾脏中滤泡辅助T(Tfh)细胞、滤泡调节T(Tfr)细胞、1型辅助T(Th1)细胞和CD4^(+)IL-10^(+)T细胞的变化;观察CIA小鼠关节和软骨的病理变化。结果与对照组比较,模型组小鼠的脾脏Tfh和Th1细胞的比例增加(P<0.05),Tfr和CD4^(+)IL-10^(+)T细胞比例无明显变化;与模型组比较,Tfh和Th1细胞在治疗1组和治疗2组的比例下降(P<0.05),Tfr和CD4^(+)IL-10^(+)T细胞的比例无明显变化。对照组小鼠关节面光滑,模型组小鼠关节有炎性细胞浸润、关节面粗糙、软骨受损的现象;PAD4-siRNA作用后,治疗1组CIA小鼠后爪的关节炎细胞浸润减少、软骨破坏程度降低;治疗2组CIA小鼠前爪和后爪的炎细胞浸润现象有所减轻,软骨损伤程度也得到了缓解。结论抑制PAD4基因的表达后,CIA小鼠脾脏Tfh和Th1细胞的相对数量下降,小鼠后爪的关节和软骨损伤得到缓解;注射感染PAD4-siRNA病毒的小鼠脾细胞,可缓解CIA小鼠前爪的病理变化。PAD4-siRNA可以通过调控小鼠脾脏T细胞亚群对CIA小鼠发挥潜在治疗价值。Objective To investigate the therapeutic effects of a small interfering RNA(siRNA)vector targeting peptidyl arginine deaminase 4(PAD4)and splenocytes infected with a PAD4-siRNA virus,on collagen-induced arthritis(CIA)mice,and to elucidate the underlying mechanisms.Methods The experiment mice were divided into four groups:control group,model group,therapy group 1 and therapy group 2,with 7 mice in each group.Control group mice were not treated.Initially,collagen-induced arthritis(CIA)mice model were established using bovine type II collagen.Model group mice were injected by PBS buffer Therapy group 1 mice were injected of PAD4-siRNA virus solution into the tail vein of the CIA mice,while therapy group 2 mice were injected of splenocytes infected with PAD4-siRNA virus via the same route.These injections were carried out once a week for a total of eight weeks.Subsequently,the alterations in T follicular helper(Tfh),T follicular regulatory(Tfr),T helper 1(Th1),and CD4^(+)IL-10^(+)T cells in the splenocytes of the mice were analyzed.Additionally,the pathological changes in the articular cartilage of the mice joints were detected.Results Comparison with control group,mice of model group exhibited a significant increase in the proportions of Tfh and Th1 cells in the spleen(P<0.05),while the proportions of Tfr and CD4^(+)IL-10^(+)T cells remained unchanged.Comparison with model group,therapy group 1 and therapy group 2 demonstrated a significant decrease in the proportions of Tfh and Th1 cells(P<0.05),with no changes were observed in the proportions of Tfr and CD4^(+)IL-10^(+)T cells.Additionally,the articular surface in the mice of control group was smooth,whereas model group showed signs of inflammatory cell infiltration,rough articular surface,and cartilage destruction.Following treatment with PAD4-siRNA,the infiltration of inflammatory cells and cartilage destruction in the hind paws of CIA mice in therapy group 1 were reduced.However,no reduction was observed in the infiltration of inflammatory cells and cartilage d

关 键 词：类风湿关节炎 肽基精氨酸脱亚氨酶4 小干扰RNA 1型辅助T细胞 滤泡辅助T细胞 胶原诱导关节炎小鼠 

分 类 号：R593.22[医药卫生—内科学]