淫羊藿苷对类风湿关节炎小鼠NLRP3炎性小体信号通路的影响  

Effect of icariin on NLRP3 inflammatory corpuscle signaling pathway in mice with rheumatoid arthritis

作　　者：雷杰[1] 张志文 贺梦吟[1] 李浩[1] LEI Jie;ZHANG Zhiwen;HE Mengyin;LI Hao(Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430000,Hubei,China)

机构地区：[1]湖北省中医院,湖北武汉430000

出　　处：《现代中西医结合杂志》2020年第29期3206-3211,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：湖北省卫计委中医药科研项目(ZY2019M044)。

摘　　要：目的探讨淫羊藿苷对类风湿关节炎小鼠的干预作用及NLRP3炎性小体信号通路的影响。方法将50只雄性DBA/1小鼠随机分为对照组、模型组、淫羊藿苷10 mg/kg组、淫羊藿苷20 mg/kg组、淫羊藿苷40 mg/kg组,每组10只。模型组和淫羊藿苷各组尾巴根部皮下注射含Ⅱ型胶原的完全弗氏佐剂诱导类风湿关节炎模型,在第21天二次免疫造模后,淫羊藿苷各组开始给予相应剂量淫羊藿苷灌胃,对照组和模型组灌胃等体积的生理盐水,均每天1次,连续3周。观察各组小鼠关节炎评分和关节肿胀度;眼球取血,采用ELISA法检测各组小鼠血清白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)水平;分离关节滑膜组织,采用HE和番红O染色观察各组小鼠关节滑膜的病理变化;采用RT-PCR检测各组小鼠滑膜组织中IL-1β和IL-18 mRNA表达水平;采用Western blot法检测各组小鼠滑膜组织中NLRP3炎性小体信号通路分子(IL-1β、Caspase-1及NLRP3)表达水平。结果首次免疫21 d后,模型组及淫羊藿苷各组小鼠的关节炎评分开始增加,模型组小鼠的关节炎评分持续增加至实验结束;从第27天开始,淫羊藿苷各组小鼠的关节炎评分与模型组比较呈剂量依赖性降低(P均<0.05)。淫羊藿苷各组关节肿胀度均明显低于模型组(P均<0.05),且呈剂量依赖性降低。模型组小鼠血清中IL-1β、IL-18水平和滑膜组织中IL-1βmRNA、IL-18 mRNA、IL-1β、Caspase-1、NLRP3表达水平均显著高于对照组(P均<0.05);淫羊藿苷各组小鼠血清中IL-1β、IL-18水平和滑膜组织中IL-1βmRNA、IL-18 mRNA、IL-1β、Caspase-1、NLRP3表达水平均显著低于模型组(P均<0.05),且呈剂量依赖性降低。病理结果显示模型组小鼠滑膜组织中出现严重的炎性细胞浸润、基质破坏及钙含量显著减少,淫羊藿苷各组炎性症状及基质破坏减轻,钙含量显著增加。结论淫羊藿苷可通过抑制NLRP3炎性小体介导的炎症反应来缓解类风湿Objective It is to explore the interventional effect of icariin on rheumatoid arthritis mice and the influence on NLRP3 inflammatory corpuscle signaling pathway.Methods 50 male DBA/1 mice were randomly divided into control group,model group,icariin 10 mg/kg group,icariin 20 mg/kg group,and icariin 40 mg/kg group,each group had 10 mice.The mice in the model group and the icariin groups were given complete Freund’s adjuvant containing typeⅡcollagen by subcutaneous injection at the base of the tail to induce rheumatoid arthritis.After the second immunization on the 21st day,each group of icariin began to be given corresponding dose of icariin by gavage,and the control group and model group were intragastrically administered with equal volume of normal saline,all once a day,treated for 3 weeks.The arthritis scores and joint swelling of the mice in each group were observed;the blood from the eyeballs was taken to detect the levels of serum interleukin-1β(IL-1β)and interleukin-18(IL-18)in the mice of each group by ELISA.The joint synovial tissue was separated,and the pathological changes of the joint synovium of the mice in each group were observed by HE and Safranin O staining;the expression level of IL-1βand IL-18mRNA in the synovial tissue of the mice in each group was detected by RT-PCR;the expression levels of NLRP3 inflammatory corpuscle signaling pathway molecules(IL-1β,Caspase-1 and NLRP3)was detected by Western Blot method.Results 21 days after the first immunization,the arthritis scores of the mice in the model group and the icariin groups began to increase,and the arthritis scores of the mice in the model group continued to increase until the end of the experiment;from the 27th day,the arthritis scores of mice in the icariin groups were decreased in a dose-dependent manner compared with the model group(all P<0.05).The joint swelling of each icariin group was significantly lower than that of the model group(all P<0.05),and it decreased in a dose-dependent manner.The levels of IL-1βand IL-18 in the se

关 键 词：类风湿关节炎 淫羊藿苷 炎性小体 炎症 

分 类 号：R-332[医药卫生]