骆驼蓬对类风湿关节炎NLRP3、TLR4信号通路的影响  

Effect of Luotuopeng(Peganum harmala L.)on NLRP3 and TLR4 Signaling in Rheumatoid Arthritis

作　　者：田新玮[1] 王静 郑琦丽 裴静[1] 陈昶[2] TIAN Xinwei;WANG Jing;ZHENG Qili;PEI Jing;CHEN Chang(The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,Xinjiang,China;Tengzhou Hospital of Traditional Chinese Medicine,Tengzhou 277500,Shandong,China)

机构地区：[1]新疆医科大学第五附属医院,新疆乌鲁木齐830011 [2]滕州市中医医院风湿免疫科,山东滕州277500

出　　处：《辽宁中医杂志》2024年第10期136-140,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：新疆维吾尔自治区自然科学基金项目(2020D01C222)。

摘　　要：目的探究骆驼蓬外敷对类风湿关节炎大鼠NLRP3、TLR4信号通路及滑膜损伤的影响。方法24只SD雌雄各半大鼠随机分组(对照组、模型组和骆驼蓬组,n=8)。对模型组和骆驼蓬组进行胶原诱导型关节炎(CIA)构建大鼠类风湿关节炎模型(14 d免疫造模)。造模完成对骆驼蓬组大鼠进行骆驼蓬外敷[0.50 g/(kg·d)],持续治疗28 d,对照组、模型组不作处理。治疗期间定期对大鼠的关节肿胀度、关节炎指数进行追踪记录。大鼠给药28 d后处死,ELISA检测其血清及滑膜组织上清液中类风湿因子(RF)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)水平;蛋白免疫印迹法(Western blot)对滑膜组织中的NLRP3信号通路分子(caspase-1、IL-1β、IL-18)和TLR4信号通路分子[Toll样受体4(TLR4)、髓样分化因子88(MyD88)、磷酸化核因子kB p65(p-NF-kB p65)、核蛋白(NF-kB p65)]及其mRNA表达水平进行检测。结果根据检测结果可知,模型组大鼠右后肢关节肿胀度(4.67±0.53)mm远大于骆驼蓬组关节肿胀度(2.78±0.38mm);模型组和骆驼蓬组关节炎指数随着试验的推进不断增加,骆驼蓬组始终低于模型组;ELISA检测发现模型组体内的RF、IL-1β、IL-6、IL-18、TNF-α水平均比对照组和骆驼蓬组显著增高(P<0.001);Western blot检测发现:模型组NLRP3信号通路分子(caspase-1、IL-1β、IL-18、IL-1βmRNA、IL-18mRNA)表达水平和TLR4信号通路分子(TLR4、MyD88、p-NF-kB p65及TLR4 mRNA)表达水平均比对照组和骆驼蓬组显著增高(P<0.001)。结论骆驼蓬外敷可以通过降低血清细胞因子水平,抑制NLRP3、TLR4信号通路,影响其蛋白及mRNA表达,缓解类风湿关节炎,降低对关节滑膜的损伤。Objective To investigate the effect of Luotuopeng(Peganum harmala L.)external application on NLRP3 and TLR4 signaling pathways and synovial injury in rats with rheumatoid arthritis.Methods Twenty-four SD rats,half male and half female,were randomly divided into control group,model group and Luotuopeng(Peganum harmala L.)group,8 rats in each group.The model group and Luotuopeng(Peganum harmala L.)group set up the collagen-induced arthritis(CIA)rat model(14 days of immune modeling).The model was completed and the rats in the Luotuopeng(Peganum harmala L.)group used Luotuopeng(Peganum harmala L.)external application[0.50 g/(kg·d)]for 28 days,and the control group and the model group were not treated.During treatment,the joint swelling and arthritis index of rats were tracked regularly.The rats were executed 28 days after administration,and enzyme-linked immunosorbent assay(ELISA)detected the levels of rheumatoid factor(RF),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in serum and synovial tissue supernatant.Western blot method detected recombinant NLR family pyrin domain containing protein 3(NLRP3)signaling pathway molecules[cysteine-requiring aspartate protease-1(caspase-1),IL-1β,IL-18]and TLR4 signaling pathway molecules[Toll-like receptor 4(TLR4),myelinoid differentiation factor 88(MyD88),phosphorylated nuclear factor kB p65(p-NF-kB p65),nuclein]and their mRNA expression levels in synovial tissues.Results According to the test results,the joint swelling of the right hind limb[(4.67±0.53)points]in the model group was much greater than that[(2.78±0.38)points]of the joint swelling of the Luotuopeng(Peganum harmala L.)group.The arthritis index of the model group and the Luotuopeng(Peganum harmala L.)group increased as the trial progressed,and the index of the Luotuopeng(Peganum harmala L.)group was always lower than that of the model group.ELISA detection found that the levels of RF,IL-1β,IL-6,IL-18 and TNF-αin the model group were significantly higher tha

关 键 词：骆驼蓬 TLR4 NLRP3 滑膜损伤 类风湿关节炎 

分 类 号：R256[医药卫生—中医内科学]