To Explore The Mechanism Of Shenggu Zaizao Pills In Treating Steroid-induced Femoral Head Necrosis Based On Network Pharmacology

Objective:The aim of this study is to predict the mechanism of Shenggu Zaizao pills in the treatment of steroid-induced osteonecrosis of the femoral head based on network pharmacology,and to explore the specific mechanism of Shenggu Zaizao pills in the treatment of steroid-induced osteonecrosis of the femoral head.Methods:1.To predict the target and molecular mechanism of Shenggu Zaizao pills in the treatment of hormone-induced femur head necrosis by network pharmacological method,and to screen the intersection target of traditional Chinese medicine and disease;The core targets for the treatment of SONFH were selected by constructing a "drug-target-disease" network and then GO and KEGG enrichment analysis were performed,followed by visualization of the obtained data.2.To explore the effect and related mechanism of Shenggu Zaizao pills containing serum on osteogenic differentiation of BMSCs based on MAPK signaling pathway.Dexamethasone was used to induce BMSCs to establish SONFH model in vitro.The optimal concentration of serum containing dexamethasone was screened by CCK-8.q RT-PCR was used to detect the gene expression levels of osteogenic factors and key factors of MAPK signaling pathway in BMSCs,and Western blot was used to detect the content of key proteins of MAPK signaling pathway.Results:1.In the TCMSP database,there were 175 active ingredients and 318 target genes of Shenggu Zaizao pills that met the screening criteria.A total of 886 disease targets related to steroid-induced osteonecrosis of the femoral head were obtained from the databases Gene Cards and OMIM,and 132 key targets were obtained after intersection of traditional Chinese medicine and disease targets.After PPI screening,six core genes were obtained: AKT1,TNF,TP53,IL6,IL1 B and JUN.GO and KEGG enrichment analysis showed that SGZZP may mediate biological processes such as signal transduction,drug response,negative regulation of apoptosis,and inflammatory response by interfering with PI3K-Akt,IL-17,TNF,and MAPK signaling pathways to treat SONFH.2.In vitro experiment: compared with NC group,the expression of Runx2,Bmp2,ERK1/2,P38 m RNA and ERK1/2,P38 protein in DXMS group decreased;Compared with DXMS group,the expressions of Runx2,Bmp2,P38 m RNA and ERK1/2,P38 protein in SGZZP group were increased.The above differences were statistically significant(P<0.05).Conclusion:1.Shengguzaizao pills regulates AKT1,TNF,TP53,IL6,IL1 B,JUN and other related targets through quercetin,luteolin,kaempferol,β-sitosterol and other active components,and then interferes with PI3K-Akt,IL-17,TNF and MAPK signaling pathways.It mediates signal transduction,drug response,negative regulation of apoptotic process,inflammation and other biological processes,so as to play a role in the treatment of SONFH.2.The expression levels of Runx2 and Bmp2 m RNA in BMSCs can be increased by activating ERK1/2/P38 MAPK signaling pathway.3.Targeting ERK1/2/P38 MAPK signaling pathway is one of the key mechanisms of Shenggu Zaizao pills in the treatment of SONFH.