摘要
目的通过观察虎杖对胶原诱导性关节炎(CIA)大鼠踝关节病理及滑膜组织、血清中过氧化物酶体增殖物激活受体-γ(PPARγ)、p65、白细胞介素17(IL-17)表达的影响,探讨虎杖抑制类风湿关节炎(RA)滑膜免疫炎性损伤的作用机制。方法采用大鼠尾根部注射牛CⅡ方法制备CIA模型,将成模大鼠按随机数字表法分为模型组、阳性对照组、虎杖2倍剂量组、虎杖常量组,另设正常对照组,每组6只。正常对照组与模型组每天予去离子水10 mL/kg灌胃,阳性对照组每天予来氟米特1.87 mg/kg灌胃,虎杖2倍剂量组、常量组每天分别以8、4 g/kg灌胃,连续干预12周。采用光镜观察各组大鼠踝关节病理改变。运用RT-PCR、Western Blot及ELISA检测技术,观察各组大鼠滑膜组织、血清中PPARγ、p65、IL-17 mRNA及蛋白表达情况。结果与正常对照组比较,模型组大鼠踝关节关节周围纤维组织增生,炎性细胞浸润;与模型组比较,虎杖常量组大鼠关节软骨、关节腔未见明显病变。与正常对照组比较,模型组PPARγ、p65、IL-17 mRNA及蛋白表达上调(P<0.01)。与模型组比较,虎杖2倍剂量组及常量组p65、IL-17 mRNA及蛋白表达均下调(P<0.01);PPARγmRNA蛋白表达水平上调(P<0.01)。结论虎杖改善CIA模型大鼠关节滑膜免疫炎性损伤的机制,可能与调节PPARγ/NF-κB信号途径相关。
Objective To observe the effects of Polygonum cuspidatum on ankle joint pathology,synovial tissue,and serum peroxisome proliferator activated receptor gamma(PPAR gamma),p65,IL-17 expression in rats with collagen-induced arthritis(CIA),and to study its mechanism for inhibiting synovial immune inflammatory injury in rheumatoid arthritis(RA).Methods CIA model was established by injecting bovine CⅡinto the tail root of rats.The rats were divided into model group,positive control group,2 times dosage group of Polygonum cuspidatum,and constant dosage group of Polygonum cuspidatum by random digit table,6 in each group.Another normal control group was set up(n=6).Deionized water 10 mL·kg-1·d-1 was administered to rats in the normal control group and the model group by gastrogavage.Leflunomide 1.87 mg·kg-1·d-1 was administered to rats in the positive control group by gastrogavage.Eight and 4 g·kg-1·d-1 Polygonum cuspidatum was respectively administered to rats in the 2 times dosage group of Polygonum cuspidatum,and constant dosage group by gastrogavage.All medication lasted for 12 successive weeks.The pathological changes of ankle joint of rats in each group were observed by light microscopy.RT-PCR,Western Blot and ELISA were used to detect the expressions of PPAR-gamma,p65 and IL-17 in synovial tissue and serum of rats in each group.ResultsCompared with the normal control group,the fibrous tissue around the ankle joint in the model group were proliferated and inflammatory cells infiltrated.Compared with the model group,there were no obvious pathological changes in the articular cartilage and articular cavity in the constant dosage group of Polygonum cuspidatum.Compared with the normal control group,mRNA and protein expressions of PPAR gamma,p65,and IL-17 in the model group were up-regulated(P<0.01).Compared with the model group,mRNA and protein expressions of p65 and IL-17 in the two Polygonum cuspidatum groups were down-regulated(P<0.01);the expressions of PPAR gamma in the two Polygonum cuspidatum groups were up-regulated(P<0.01).Conclusion The mechanism of Polygonum cuspidatum for improving synovial immune inflammatory injury in CIA rats might be related to regulating PPARgamma/NF-kappa B signaling pathway.
作者
杨蕾
张正菊
相瑞阳
顾文
张红红
何毓玺
王达利
刘慧
马卫国
孟凤仙
YANG Lei;ZHANG Zheng-ju;XIANG Rui-yang;GU Wen;ZHANG Hong-hong;HE Yu-xi;WANG Da-li;LIU hui;MA Wei-guo;MENG Feng-xian(Department of Rheumatology,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing(100078);Department of Rheumatology,Beijing Hospital of Chinese Medicine,Beijing(100010);Department of Rheumatology,Shunyi Hospital of Traditional Chinese Medicine,Beijing(101300))
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2019年第5期591-596,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金面上项目(No.51772032)
北京中医药大学基本科研业务费在读研究生项目(No.2018-JYB-XS218)