摘要
目的研究二妙散对类风湿关节炎(RA)调控基因Toll样受体(TLR4)和重组牛磷酸肌醇3激酶A(PI3KA)表达的影响。方法通过构建Wistar大鼠胶原诱导性关节炎(CIA)模型,不同浓度二妙散灌胃治疗,酶联免疫吸附试验(ELISA)检测血清中炎症因子的表达,苏木精-伊红(HE)染色进行病理学分析,实时荧光定量聚合酶链反应(qRT-PCR)分析TLR4和PI3KA的表达特性。结果二妙散组与CIA模型组相比,脾脏指数差异无统计学意义(P>0.05);CIA模型组与对照组相比,脾脏指数显著降低,差异有统计学意义(P<0.05);二妙散组滑膜组织炎性细胞较少;较正常组白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α表达量极显著降低,差异有统计学意义(P<0.01,P<0.05),较模型组显著降低,差异有统计学意义(P<0.05);随二妙散浓度增加IL-37表达量显著增加,差异有统计学意义(P<0.05,P<0.01)。模型组大鼠关节中IL-6、TLR4和PI3KA mRNA水平表达量极显著高于对照组和甲氨蝶呤组,差异有统计学意义(P<0.01)。结论本实验成功构建CIA大鼠模型,TLR4和PI3KA在不同实验组大鼠关节组织中均有不同程度的表达,说明TLR4和PI3KA参与CIA大鼠炎性反应的形成,介导RA炎性因子的形成和发展,二妙散对于减少炎症因子和增加抑炎因子的表达具有重要作用,具体作用机制需进一步研究证实。
Objective To determine the effects of of Er-Miao-San(EMS)on the expression of rheumatoid arthritis(RA)regulatory genes TLR4 and PI3KA.Methods Wistar rats models of collagen-induced arthritis(CIA)were established,and subjected to EMS gavage at various doses.The expression of inflammatory factors in serum was detected by ELISA.Pathological analysis was performed by HE staining,and the expression characteristics of TLR4 and PI3KA in joints of rats was analyzed by qRT-PCR.Results Compared with the CIA model group,rats on EMS did not show significant differences in spleen index(P>0.05).Compared with the normal group,the CIA models showed significantly lower spleen index with statistical difference(P<0.05).Compared with the normal group,the EMS group showed fewer inflammatory cells in the synovial tissue,and remarkably reduced expression of IL-6 and TNF-α,with statistically significant differences(P<0.01,P<0.05),as were these compared with the model group(P<0.05).With the increase of EMS doses,the expression of IL-37 increased significantly(P<0.05,P<0.01).The expression levels of IL-6,TLR4 and PI3KA mRNA in the joints of the model group were significantly higher than those in the control group and methotrexate group,which was statistical difference(P<0.01).Conclusion In this experiment,CIA rat models were successfully established.The expression of TLR4 and PI3KA in joint tissue of rats varies across groups,indicating that TLR4 and PI3KA participate in the development of inflammatory reactions in CIA rats,and mediate the production of inflammatory factors and disease progression in RA.EMS plays an important role in ameliorating inflammatory factors and enhancing the expression of anti-inflammatory factors,although the exact mechanism is yet to be confirmed by further research.
作者
李振
郝慧琴
高玉亭
王泽
刘进
芦文静
Li Zhen;Hao Huiqin;Gao Yuting;Wang Ze;Liu Jin;Lu Wenjing(College of Basic Medical Sciences,Shanxi University of Chinese Medicine,Jinzhong 030619,China)
出处
《中国药物与临床》
CAS
2020年第10期1585-1588,共4页
Chinese Remedies & Clinics
基金
国家自然科学基金青年科学基金(81904034)
山西省面上青年基金(201901D211534)
山西省高等学校科技创新项目(201804001)
山西省卫生健康委青年基金(2018001)
。
