Exploration of action mechanism of sodium cromolyn in preventing acute pulmonary hypertension combined network pharmacology with molecular docking technology
Objective To explore the action mechanism of mast cells(MCs)degranulation inhibitor sodium cro-molyn(SCG)in preventing acute pulmonary hypertension(APH)combined network pharmacology with molecular docking technology.Methods ①The target genes of cromolyn for APH were obtained from Swiss Target,TargetNet,UniProt,OMIM,GeneCards and NCBI gene databases.Venny 2.1 online tool was adopted to draw the Venn diagram and obtain intersection genes.A protein-protein interaction(PPI)network was constructed through String database.Topological analysis of PPI network was carried out by using software Cytoscape.Gene Ontology(GO)function anal-ysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was carried out by using DAVID database,and relevant signal pathways were screened out.Molecular docking analysis was carried out by using soft-ware Autodock Vina.(2)SD rats were given SCG(100 mg/kg,ig,Bid,3 d)pre-treatment.The acute hypoxia animal model was replicated by using hypobaric chamber(simulated altitude of 7,000 m,12 h).SD rats were randomly di-vided into hypoxia control group(HC group,12 rats)and hypoxia SCG treatment group(HSCG group,12 rats).The el-evation of hypoxic chamber was lowered from 7,000 m to 3,500 m.The pulmonary arterial pressure(PAP)was moni-tored by external carotid vein intubation.The expression levels of FcεR Ⅰ,SYK,mTOR,p-mTOR(ser 2448)in lung tissue of SD rats were detected by Western Blot(WB)assay.Results ①FcεR Ⅰ and mTOR signaling pathways as well as core proteins including FcεR Ⅰ,SYK and mTOR were selected on the basis of network pharmacological anal-ysis.FcεR Ⅰ,SYK and mTOR were docked with cromolyn respectively,and all showed good binding activity and sta-ble conformation.②mPAP results of SD rats:mPAP decreased in HSCG group compared with HC group(P＜0.05).③ WB results of lung tissue:Compared with HC group,the protein expression of FcεR Ⅰ,SYK,mTOR and p-mTOR(ser2448)in lung tissue of SD rats in HSCG group decreased(P＜0.05),and p-mTOR(ser2448)/mTOR also de-clined(P＜0.05).Conclusion After SCG pre-treatment,the protein expression of FcεR Ⅰ,SYK,mTOR,p-mTOR(ser2448)and p-mTOR(ser2448)in MCs in lung tissue of SD rats with acute hypobaric hypoxia stress could be re-duced.The activation level of FcεR Ⅰ and mTOR signaling pathway could be decreased as well.Then,the activated degranulation process of MCs in lung tissue could be inhibited,and the release of vasoconstrictive active substances could be reduced,thereby achieving the prevention of hypoxic APH.
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