摘要
OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.
OBJECTIVE To investigate the anti-rheumatoid arthritis（RA） effect of Escin combined with low dose of GCs（dexamethasone, Dex） and its underlying mechanism. METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro. In vivo experiment: rats were randomly divided into model group（AIA）, dexamethasone high dose(Dex, 0.2 mg·kg-1) group, dexamethasone low dose(Dex, 0.05 mg·kg-1)group, Escin 10 mg·kg-1 group, Dex 0.05+Escin group, 10 rats in each group, another 10 were used as normal control group. The vehicle and the corresponding drug were administered intragastrically（ig） daily for 14 d. In vitro experiment: LPS was used to stimulate RAW264.7 macrophages for inflammatory models, which were divided into control group, LPS group, Dex with high dose(50 nmol·L-1)group, and Dex with low dose(12.5 nmol·L-1) group. In the Escin 10 μmol·L-1 group and the Dex+Escin(12.5 nmol·L-1+10 μmol·L-1)group, the corresponding drugs were added to each well. After 2 h, LPS was added to induce inflammation. RESULTS Escin combined with low dose Dex significantly decreased arthritic index, serum IL-6 and TNF-α, improved paw swelling, and ameliorated the joint pathology immune organ pathology significantly. Gene chip results revealed that Nr3 c1（GR） altered significantly. And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro. Furthermore, Escin combined with low dose Dex also significant increase GR mRNA expression. However, when suppression of GR by its specific inhibitor, the anti-RA effect of Escin combined with low dose Dex was abolished. CONCLUSION Escin combined with Dex reduces the dose of Dex, and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex. This combination might be attributed to GR activation. This study might provide a new combination drugs for the treatment of RA.
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2019年第9期749-750,共2页
Chinese Journal of Pharmacology and Toxicology
基金
National Natural Science Foundation of China(81873039
81973547)
Natural Science Foundation of Shandong Province(ZR2017MH068)
