Effect of Wutou Decoction(乌头汤)Combined with Methotrexate on Rheumatoid Arthritis in Rats and Its Correlation with p38MAPK Pathway
Objective:To investigate the effect of Wutou decoction(WTD)combined with methotrexate on rheumatoid arthritis(RA)in rats and its correlation with the p38MAPK pathway.Method:Totally 75 male Wistar rats were randomly divided into blank group,RA model group,methotrexate group,WTD group,and WTD+ methotrexate group,with 15 rats in each group.Except for the blank group,the rats were established model of collagen induced arthritis(CIA)by subcutaneous injection of Freund's adjuvant and bovine type Ⅱ collagen into the plantar surface in other groups.Rats were given intragastric administration of methotrexate in the methotrexate group,WTD in WTD group,WTD and methotrexatein in WTD+methotrexate group,and the same amount of physiological saline in blank group and RA group.The scores of ankle joint structure and pathological changes were evaluated in 28 days.Polymerase chain reaction(PCR)was used to detect the expression levels of type Ⅱcollagen mRNA and p38MAPK mRNA in chondrocytes.Western blotting was used to detect the expression level of p38MAPK protein in synovial tissue,and enzyme linked immunosorbent assay(ELIAS)was used to detect serum TNF-α and IL-6 levels.Results:The RA model group,methotrexate group,WTD group,and WTD+ methotrexate group showed higher Pelletier and Mankin scores than blank group(P<0.05);The methotrexate group,WTD group and WTD+methotrexate group showed lower Pelletier and Mankin scores than RA model group(P<0.05);The WTD+methotrexate group showed lower Pelletier and Mankin scores than WTD group and methotrexate group(P<0.05).The RA model group showed lower relative expression level of type Ⅱ collagen mRNA than blank group(P<0.05),while higher relative expression level of p38MAPK mRNA,p38MAPK protein in synovial tissue,serum TNF-α and serum IL-6 than blank group(P<0.05).The methotrexate group,WTD group and WTD+methotrexate group showed higher relative expression level of type Ⅱ collagen mRNA than RA model group(P<0.05),while lower relative expression level of p38MAPK mRNA,p38MAPK protein in synovial tissue,serum TNF-α and serum IL-6 than RA model group(P<0.05).The WTD+methotrexate group showed higher relative expression level of type Ⅱ collagen mRNA than WTD group and methotrexate group(P<0.05),while lower relative expression level of p38MAPK mRNA,p38MAPK protein in synovial tissue,serum TNF-α and serum IL-6 than WTD group and methotrexate group(P<0.05).Pearson correlation analysis showed that serum TNF-α and IL-6 was positively correlated with the relative expression of p38MAPK mRNA in chondrocytes(P<0.05).Conclusion:The combination of Wutou decoction and methotrexate shows good therapeutic effect on rheumatoid arthritis in rats,and its mechanism may be related to the inhibition of the p38MAPK signaling pathway.
万方数据
维普
