紫杉醇单独或与甲氨蝶呤联合用药对关节炎的治疗作用及其机制  

Therapeutic Effect and Mechanism of Paclitaxel Alone or in Combination with Methotrexate on Arthritis

作　　者：盛正和[1] 曾健[1] 黄文 李玲[2] 李斌斌 吕超 颜凡棋 Sheng Zhenghe;Zeng Jian;Huang Wen;Li Ling;Li Binbin;Lv Chao;Yan Fanqi(Department of Traditional Chinese Medicine, Liuzhou People'sHospital, Liuzhou 545006, China;Graduate School, Guangxi University of Chinese Medicine, Nanning 530001, China)

机构地区：[1]柳州市人民医院中医科,柳州545006 [2]广西中医药大学研究生院,南宁530001

出　　处：《成都医学院学报》2020年第4期468-473,共6页Journal of Chengdu Medical College

基　　金：广西柳州市科技攻关项目(No:2015J030522)。

摘　　要：目的对紫杉醇(PTX)、甲氨蝶呤(MTX)或者PTX和MTX联合用药(PTX+MTX)的关节炎治疗作用进行比较,并对其机制进行研究。方法经胶原诱发建立SD大鼠类风湿关节炎(RA)模型,14 d后四肢红肿为胶原诱导性关节炎(CIA)模型构建成功。实验随机分为7组(n=10):空白对照组、模型组、MTX治疗组(1 mg/kg)、PTX低中高剂量治疗组(1.5、2.5、3.5 mg/kg)和MTX+PTX联合治疗组(MTX 1 mg/kg,PTX 3.5 mg/kg)。HE染色分析踝关节炎症情况,免疫组织化学方法检测IL-1β和IL-6的表达,蛋白质印迹技术检测滑膜组织中TLR4和p-NFκBp65蛋白的表达,ELISA检测血清中IL-1β、IL-6、IL-12、MMP-3、TNFα蛋白因子含量的变化。结果与模型组相比,各治疗组均能不同程度的减轻炎性细胞浸润和水肿充血现象,一定程度上降低了IL-6和IL-1β阳性细胞数量,同时降低了TLR4、p-NFκBp65蛋白表达量以及血清中的MMP-3、IL-12、IL-6、IL-1β和TNFα的含量,且均为PTX高剂量组降低更明显(P<0.05)。结论PTX与MTX均对RA具有治疗作用,两药联合应用疗效弱于PTX单药。PTX和MTX通过抑制CIA模型滑膜组织中TLR4和p-NFκBp65蛋白的表达可能是发挥药效的机制。Objective To compare the therapeutic effect of paclitaxel(PTX)alone or in combination with methotrexate(MTX)on arthritis and analyze their mechanisms.Methods The rheumatoid arthritis models of Sprague Dawley(SD)rats were established by collagen induction,and the collagen-induced arthritis(CIA)models were successfully established with limb swelling 14 days later.Those models were randomly divided into 7 groups including the blank control group,model group,MTX treatment group(with 1 mg/kg MTX),low-,medium-and high-dose PTX treatment groups(with 1.5,2.5 and 3.5 mg/kg PTX,respectively)and MTX+PTX combined treatment group(with 1 mg/kg MTX and 3.5 mg/kg PTX),with 10 rats in each group.The inflammation of ankle joints was analyzed by HE staining.The expression of IL-1βand IL-6 was detected by immunohistochemistry.The expression of TLR4 and p-NFκBp65 protein in synovial tissues was determined by Western blot.And the changes of serum IL-1β,IL-6,IL-12,MMP-3 and TNFαprotein factors were assayed by ELISA.Results Compared with the model group,inflammatory cell infiltration,edema and hyperemia were alleviated in varying degrees,and the amount of IL-6 and IL-1βpositive cells,the expression of TLR4 and p-NFκBp65 protein and the content of serum MMP-3,IL-12,IL-6,IL1-βand TNFαwere decreased to some extent in the other treatment groups with the best therapeutic effect in the high-dose PTX treatment group(P<0.05).Conclusion Both PTX and MTX have therapeutic effect on rheumatoid arthritis and the effect of combining the two drugs is weaker than that of PTX alone.PTX and MTX may play a pharmacodynamic role by inhibiting the expression of TLR4 and p-NFκBp65 protein in the synovial tissue of CIA models.

关 键 词：紫杉醇 甲氨蝶呤 关节炎 TLR4 p-NFκBp65 

分 类 号：R593[医药卫生—内科学]