RESUMO
Objective: To investigate the molecular mechanism of Salvia miltiorrhiza (SM) in the treatment of retinitis pigmentosa (RP) by interfering with the expression of characteristic genes and key protein in Müller cells (MC) based on the methods of network pharmacology and bioinformatics. Methods: Retrieval and screening of active ingredients and therapeutic targets of SM in blood was performed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Differentially expressed genes of MC in normal and RP mice were obtained by searching GEO database. RP-related gene targets were retrieved through disease database. Cytoscape was used to construct protein-protein interaction networks of differentially expressed MC genes, disease targets and component targets and the intersection was extracted. Gene Ontology and KEGG signaling pathway analysis of characteristic genes were carried out by DAVID. CytoHubba was used to analyze and screen the key protein targets. Results: A total of 202 chemical constituents related to SM were retrieved, 65 active ingredients were screened according to ADME parameters, of which 13 were active ingredients in blood. A total of 117 possible targets were obtained by further searching and matching. A total of 242 differentially expressed genes in MC of normal and RP mice were obtained from chip data. A total of 206 targets closely related to RP were obtained from disease databases. A total of 85 characteristic genes of SM affecting MC in RP pathological process were extracted and intersected. These genes were mainly involved in transcriptional regulation, apoptotic signaling pathway regulation, DNA nuclear replication regulation and other biological processes. Molecular functions mainly include transcriptional coactivator activity, protein kinase activity, core promoter binding, etc. They were enriched in nuclear, nucleoplasm, transcription factor complex, Rb-E2F complex and other regions. The signaling pathways involved include splicer signaling pathway, actin cytoskeleton signaling pathway, cell cycle signaling pathway and so on. A total of eight key protein targets of SM on MC in RP pathological process were analyzed and screened. Conclusion: The substance basis of the pharmacodynamics of SM is 13 chemical constituents, such as cryptotanshinone, luteolin, tanshinone IIA, etc. The MC characteristic genes involved in the pathological process of RP intervened by SM are related to spliceosome signaling pathway, actin cytoskeleton signaling pathway, cell cycle regulation pathway, etc. The key targets include eight protein such as RB1, E2F1, TFDP1, etc.