基于JAK/STAT信号通路探讨红茴香注射液对类风湿关节炎小鼠的作用机制  

To investigate the mechanism of Illicium henryi injection on rheumatoid arthritis based on JAK/STAT signaling pathway

作　　者：张慧杰 柴立民[1] 刘娟[1] 张萍心 李晋玉[1] 李东阳 孙嵩 ZHANG Huijie;CHAI Limin;LIU Juan;ZHANG Pingxin;LI Jinyu;LI Dongyang;SUN Song(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《北京中医药大学学报》2022年第3期267-274,共8页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家中医药管理局国家中医临床研究基地业务建设第二批科研专项(No.JDZX2015191)。

摘　　要：目的探讨红茴香注射液治疗类风湿关节炎的作用及机制。方法32只雄性DBA/1小鼠随机分为正常组、模型组、来氟米特组及红茴香注射液组,每组8只。采用尾根部及背部多点注射牛Ⅱ型胶原蛋白乳化剂建立胶原诱导性关节炎(CIA)小鼠模型。正常组和模型组以生理盐水、来氟米特组以来氟米特(3 mg/kg)灌胃,红茴香注射液组腹腔注射红茴香注射液(0.3 mL/kg),每日1次,连续28 d。药物干预后每7天进行1次关节炎性评分,测量足跖关节肿胀厚度。28 d后取材,采用HE染色法观察踝关节组织病理学形态并进行组织病理学评分;采用Safranin O染色法观察关节软骨破坏程度并进行染色缺失评分;Western blot法测定滑膜组织中酪氨酸激酶2(JAK2)和信号转导及转录激活蛋白6(STAT6)、磷酸化酪氨酸激酶2(p-JAK2)、磷酸化信号转导及转录激活蛋白6(p-STAT6)的表达水平。结果与模型组比较,红茴香注射液组关节炎指数评分降低(P<0.05),足跖关节厚度减小(P<0.05,P<0.01),关节病理改变评分及滑膜中JAK2、STAT6蛋白表达量及其磷酸化水平均降低(P<0.05,P<0.01)。结论红茴香注射液对CIA小鼠具有抗炎及免疫调节作用,其作用机制可能是通过抑制JAK2、STAT6相关蛋白磷酸化表达,调控JAK/STAT信号通路。Objective We aimed to investigate the mechanisms underlying the effects of Illicium henryi injection on rheumatoid arthritis(RA).Methods Male DBA/1 mice were randomly divided into:(i)the normal group,(ii)the model group,(iii)the leflunomide group,and(iv)the Illicium henryi injection group(n=8 mice per group).A collagen-induced arthritis(CIA)mouse model was established by multipoint injection of bovine typeⅡcollagen emulsifier in the tail and back.Mice in the normal group and model group were given normal saline.Mice in the leflunomide group were given leflunomide(3 mg/kg)by gavage.Mice in the Illicium henryi injection group were intraperitoneally injected with Illicium henryi injection(0.3 mL/kg)once a day for 28 consecutive days.Joint inflammatory scores were recorded every 7 days after the intervention to measure the degree of joint swelling.After 28 days,HE staining was used to observe the histopathological morphology and record the histopathological score of the ankle joint.Safranin O staining was used to observe the degree of damage to articular cartilage and score the loss of staining.The protein expression levels of JAK2,p-JAK2,STAT6,and p-JAK6 in synovial tissues were determined by Western blot.Results Compared with the model group,the arthritis index score was lower in the Illicium henryi injection group(P<0.05),the foot joint was thinner(P<0.05,P<0.01),the pathological changes of the joint were less severe,and the expression and phosphorylation of JAK2 and STAT6 in synovium were lower(P<0.05,P<0.01).Conclusion Illicium henryi injection has anti-inflammatory and immunomodulatory effects on CIA mice through inhibiting the phosphorylation and expression of JAK2 and STAT6 and regulating the JAK/STAT signaling pathway.

关 键 词：类风湿关节炎 红茴香注射液 滑膜组织 JAK/STAT信号通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]