The Effect Of Ursolic Acid On The Expression Of RANKL, RANK, OPG, MMPs MRNA In The Joints Of CIA Rats

Objective : This project explores the effect of ursolic acid(UA)on Collagen-Induced Arthritis(CIA)rat nuclear factor ?B receptor activating factor ligand(Receptor Activator of NF-?B Ligand,RANKL),Receptor Activator of NF-?B(RANK),Osteoprotegerin(OPG),Matrix metalloproteinases(MMPs)m RNA expression,with a view to partially elucidating UA inhibition of CIA rat joints The molecular mechanism of inflammation.Methods: 70 female SD rats were taken.Six rats were randomly selected as a blank control group.The rest of the rats replicated the CIA model.The CIA rats successfully modeled were randomly divided into a CIA model group,a low-dose ursolic acid group(50 mg/kg/d),and a high ursolic acid.Dose group(100mg/kg/d),methotrexate group(Methotrexate,MTX)(0.9mg/kg/w),ursolic acid(50mg/kg/d)+ methotrexate group(0.9mg/kg /w),6 per group.From the 12 th day of the initial immunization,the ursolic acid group was given ursolic acid,the methotrexate group was given methotrexate,and the ursolic acid combined with methotrexate group was given ursolic acid plus methotrexate.Stomach,rats in the blank group and CIA model group were given intragastric administration of equal volume of normal saline respectively.The rats were sacrificed after 30 days of initial immunization.The right hind foot inflammation joints were removed,total RNA was extracted,and RANKL and RANK were detected by RT-PCR.,OPG,MMP1,MMP9,MMP13 m RNA expression in joint homogenate of rats in each group.Results:(1)Compared with the blank group,the expression of RANKL and OPG m RNA in the model group was significantly increased(P<0.01).Compared with the model group,the expression of RANKL in ursolic acid low-dose group,ursolic acid high-dose group,methotrexate group,and ursolic acid + methotrexate group was significantly reduced(P<0.05 and P<0.01),and The expression of RANKL in the ursolic acid + methotrexate group was significantly lower than that in the methotrexate group(P<0.05);different doses of ursolic acid group,methotrexate group,ursolic acid + methotrexate group and model group In comparison,the difference in OPG expression was not statistically significant(P>0.05).There was no significant difference in the expression of RANK among the groups(P>0.05).(2)Compared with the blank group,the expression of MMP1 and MMP9 m RNA in the model group was significantly up-regulated(P<0.01),and the expression of MMP13 m RNA in the model group was up-regulated(P<0.05 and P<0.01).Compared with the model group,the expressions of MMP1 and MMP9 in ursolic acid low-dose group,ursolic acid high-dose group,methotrexate group,ursolic acid + methotrexate group were significantly reduced(P<0.05 and P<0.01);Compared with the model group,there was no significant difference in the expression of MMP13 in the low-dose ursolic acid group,the high-dose ursolic acid group,and the methotrexate group(P>0.05),but the expression of MMP13 in the ursolic acid + methotrexate group was significant Lower than the model group(P<0.05).Conclusion:(1)The therapeutic effect of UA on arthritis and bone protection of CIA rats,the molecular mechanism may be related to the inhibition of RANKL,MMP1,MMP9 m RNA expression.(2)UA combined with MTX can enhance the inhibitory effect of MTX on MMP13 m RNA.The results suggest that UA and MTX have a synergistic effect on the treatment of arthritis in rats.