Discussion On The Mechanism Of Huangqi Guizhi Wuwu Decoction In Treating Rheumatoid Arthritis Complicated With Sarcopenia Based On UPS

Objective: To verify the efficacy of Huangqi Guizhi Wuwu decoction in the treatment of rheum arthritis(RA)combined with sarcopenia and to explore its mechanism of action,so as to provide data support for clinical treatment.Methods: 1.To screen the targets and related pathways of Huangqi Guizhi Wuwu decoction in the treatment of RA with sarcopenia by network pharmacology.To investigate the feasibility and effectiveness of collagen-induced arthritis(CIA)rat model of rheumatoid arthritis(RA)combined with sarcopenia.3.Huangqi Guizhi Wuwu decoction was used to treat CIA rats,methotrexate and astragalside ⅳ were used as positive control group,body weight,muscle strength,limb swelling degree,skeletal muscle mass,fiber area and the ubiquitin-proteasome proteolytic system,and the body weight,muscle strength,limb swelling degree,skeletal muscle mass,fiber area and the ubiquitinproteasome proteolytic system were measured.UPS)related gene muscle atrophy box of F(muscle atrophy F-box atrogin-1,MAFbx/atrogin-1),muscle specific ring finger protein 1(muscle specific ring finger protein 1.MURF1)and nuclear factor k B(NF-κB)were used as observation indicators to verify its efficacy and discuss the mechanism of Huangqi Guizhui Wuwu decoction in the treatment of RA with sarcopenia.Results: 1.Network pharmacology study showed that Huangqi Guizhi Wuwu Decoction can inhibit RA inflammatory response and subsequent activation of UPS signaling system through JAK/STAT and PI3K-Akt signaling pathways,and regulate PI3K-Akt signaling pathway to delay RA synovial hyperplasia and promote skeletal muscle hypertrophy to achieve the aim of treating RA complicated with sarcopenia.2.CIA rat model as a model of rheumatoid arthritis with sarcopenia: The joint score of CIA rats increased,and the levels of peripheral inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)increased.Joint sections showed synovial hyperplasia,bone erosion and inflammatory cell infiltration.Muscle fiber sections showed muscle fiber necrosis and lysis,intramuscular fat infiltration,inflammatory cell infiltration,and decreased muscle fiber area.The inflammation and skeletal muscle state of CIA rats are consistent with the morphology of RA sarcopenia,which can be used as an effective model for the study of RA sarcopenia.3.Effect and mechanism of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid joint with inflammatory sarcopenia:According to the joint score,both the Huangqi Guizhi Wuwu decoction group and the methotrexate group improved the joint swelling of rats,but the astragaloside ⅳ group had a poor therapeutic effect.The levels of IL-1,IL-6 and TNF-α in the treatment group and methotrexate group were lower than those in the model group(P < 0.05).Compared with the model group,the astragaloside ⅳ group had a significantly lower level of IL-1β(P < 0.05),and there was no significant difference in IL-6 and TNF-α.Skeletal muscle strength: compared with the model group,Huangqi Guizhi Wuwu decoction showed significant differences on days 7,14,21 and 28 after gavage;In astragaloside ⅳ group,there were differences on the 7th day after gavage,and significant differences on the 14 th,21st and 28 th day.There was no difference in muscle strength in methotrexate group during the whole process.Skeletal muscle mass: compared with the model group,the muscle mass of soleus,gastrocnemius and quadriceps femoris in the Huangqi Guizhi Wuwu decoction group was significantly different,and there was no significant difference in the tibialis anterior muscle mass.Compared with the blank group,the gastrocnemius and tibialis anterior muscles showed significant differences,while the quadriceps femoris and soleus muscles showed no significant difference.The muscle mass of the methotrexate group was significantly different from that of the model group,and the muscle mass of the quadriceps femoris was significantly different,and there was no significant difference in the rest of the skeletal muscles.There was no significant difference in skeletal muscle mass between astragaloside ⅳ group and model groupReal-time PCR showed that compared with the model group,the expressions of MAFbx/atrogin-1,MURF1 and NF-κB in the Huangqi Guizhi Wuwu Decoction group and methotrexate group were decreased,and there were significant differences among the three groups of methotrexate,and the expressions of MAFbx/atrogin-1 and MURF in the Huangqi Guizhi Wuwu decoction group were significantly different.There was no significant difference in the data between the three groups of astragaloside ⅳ group and the model group.Conclusion: Huangqi Guizhi Wuwu Decoction can effectively alleviate joint swelling,reduce peripheral serum proinflammatory cytokines,inhibit the UPS pathway,and restore skeletal muscle function and quality in rats with CIA.It can effectively treat rheumatoid arthritis combined with sarcopenia.