Mechanisms of action of repair after aspirin related gastric mucosal injury based on network pharmacology and immunohistochemical staining

GUO Hongwei; NI Xiaohan; PAN Yuanming; CHENG Yanli

doi:10.3969/j.issn.2097-1753.2023.05.009

Abstract：Objective To find out about the molecular mechanisms of repair after aspirin related gastric mucosal injury based on network pharmacology and immunohistochemical staining assay.Methods The SwissTargetPrediction database and DrugBank database were used to predict the target genes of aspirin,and the GeneCards database was searched to obtain the genes involved in gastric mucosal repair.The intersection targets of the two databases were collected.A protein-protein interaction network was constructed by the STRING database.The hub genes were analyzed for KEEG signal pathways and GO enrichment by using the DAVID database.Immunohistochemical staining was applied to verify the expression of a core gene in aspirin related human gastric mucosal lesions.Results It was found that 56 hub genes were involved in the repair after aspirin related gastric mucosal injury,including the key gene PCNA.The PPI network showed that PCNA mainly interacted with CCNA2 and HDAC1.KEGG pathway analysis found that PCNA participated in the related signal pathways,including cell cycle and DNA replication.GO enrichment showed that the intersection target proteins were mainly located in the nucleus.The main molecular functions of PCNA included binding to damaged DNA and histone acetyltransferase.The biological processes involved included negative transcriptional regulation of RNA polymerase Ⅱ promoter,cell reaction to hydrogen peroxide and DNA replication.Immunohistochemical staining confirmed that the expression of PCNA was up-regulated in aspirin related human gastric mucosal Lesions(Z=3.974,P＜0.001).The expression of PCNA in aspirin related superficial active gastritis and ulcerative lesions was significantly higher than in acute erosive hemorrhagic gastritis(H=13.935,P=0.001).Conclusions The repair process after aspirin related gastric mucosal injury involves multiple targets and multiple signal pathways.The interaction of PCNA with CCNA2 and HDAC1 is involved in the repair after aspirin related gastric mucosal injury,and the repair mechanism is more evident in aspirin related superficial active gastritis and gastric ulcer lesions.