线粒体分裂抑制剂1对胶原诱导性关节炎小鼠疾病进展的抑制作用和机制  

Mitochondrial division inhibitor-1 inhibits disease progression of collagen induced arthritis in mice and its mechanism

作　　者：王晓艳 陈祝锋 方瑜[1] 周瑞[2] 高飞 WANG Xiaoyan;CHEN Zhufeng;FANG Yu;ZHOU Rui;GAO Fei(Department of Diagnosis,Shanxi University of Chinese Medicine,Xianyang 712046,China;不详)

机构地区：[1]陕西中医药大学诊断学教研室,咸阳712046 [2]陕西中医药大学陕西中药资源产业化省部共建协同创新中心/秦药特色资源研究开发国家重点实验室(培育),咸阳712046 [3]陕西中医药大学整合医学研究院,咸阳712046 [4]中国人民解放军空军军医大学唐都医院骨科

出　　处：《浙江医学》2021年第18期1968-1970,1978,I0003,共5页Zhejiang Medical Journal

基　　金：陕西省重点研发计划项目(2017SF-364);国家自然科学基金青年科学基金项目(81803946)。

摘　　要：目的探讨线粒体分裂抑制剂1(Mdivi-1)对胶原诱导性关节炎(CIA)小鼠疾病进展的抑制作用和机制。方法应用DBA/1小鼠构建CIA小鼠模型,采用随机数字表法分为二甲基亚砜(DMSO)组和Mdivi-1组。DMSO组小鼠给予1%DMSO(DMSO∶0.9%氯化钠注射液=1∶100稀释)腹腔注射,0.5 ml/只;Mdivi-1组小鼠给予Mdivi-1(0.2 mg Mdivi-1溶于5μl DMSO中,然后用0.9%氯化钠注射液稀释100倍)腹腔注射,0.5 ml/只;持续10 d。第28~37天对两组小鼠进行关节炎评分,第38天采用HE染色观察小鼠膝、踝关节滑膜组织炎症细胞浸润程度,免疫组化染色评估两组小鼠关节滑膜组织叉头状转录因子3(Foxp3)、IL-17、IL-10的阳性细胞数目百分比。结果Mdivi-1组小鼠第31、33、34、35、36、37天关节炎评分均低于DMSO组,差异均有统计学意义(均P<0.05)。Mdivi-1组小鼠膝、踝关节局部滑膜组织炎症程度较DMSO组明显减轻,Foxp3、IL-10的阳性细胞数目百分比均高于DMSO组,IL-17的阳性细胞数目百分比低于DMSO组,差异均有统计学意义(均P<0.05)。结论Mdivi-1通过抑制关节滑膜局部Th17的表达,促进调节性T细胞的表达,抑制CIA病变的进展。Objective To explore the role of mitochondrial division inhibitor-1(Mdivi-1)in inhibiting disease progression of collagen induced arthritis(CIA)in mice.Methods The CIA model was induced in 16 DBA/1 mice,and the animals were randomly divided into dihydroethidium(DMSO)and Mdivi-1 groups with 8 mice in each group.The 1%DMSO(DMSO∶saline=1∶100,0.5 ml/mice)or Mdivi-1(0.2 mg Mdivi-1 dissolved in 5μl DMSO,and then diluted 100 times by saline,0.5 ml/mice)were injected intraperitoneally for ten days,respectively.On day 28-37,the arthritis score was assessed in the two groups.HE staining was used to observe the infiltration of inflammatory cells in synovial tissue of knee and ankle joints on day 38.Immunohistochemistry was used to evaluate the expression of forkhead box protein 3(Foxp3),IL-17 and IL-10.Results On day 31,33,34,35,36,37,the arthritis scores in Mdivi-1 group were significantly lower than those in DMSO group.Compared with DMSO group,the degree of synovitis in Mdivi-1 group was significantly reduced,the expression of Foxp3 and IL-10 was higher than that in DMSO group,the expression of IL-17 was lower than that in DMSO group(all P<0.05).Conclusion Mdivi-1 can promotes the expression of regulatory T cells(Tregs)and inhibits disease progression in CIA mice by inhibiting Th17 cell expression.

关 键 词：线粒体分裂抑制剂-1 胶原诱导性关节炎 免疫组化染色 

分 类 号：R593.22[医药卫生—内科学]