Effect And Mechanism Of Aurantii Fructus Immaturus And Naringin On Treatment Postoperative Peritoneal Adhesion

Objective To explore the preventive and therapeutic effects of Aurantii Fructus Immaturus(AFI)and naringin on postoperative peritoneal adhesion,and to explore the relevant mechanism of naringin in the treatment of peritoneal adhesion based on network pharmacology.Method The rat model of postoperative peritoneal adhesion was established by cecal scraping method.After 24 hours of operation,the rats were randomly divided into six groups.and were given different doses of alcohol extract of AFI(1.58 g/kg/d,3.15g/kg/d,6.3 g/kg/d),continuous administered for 7 days;Related factors were detected by hematoxylin-eosin(HE)staining,immunohistochemistry and enzyme-linked immunosorbent assay;Obtain the main components and related targets of AFI,collect the action targets of diseases,obtain the intersection targets of diseases and compounds,and screen more compounds in AFI that directly act on the peritoneal adhesion targets of diseases for experimental verification;PPI network was constructed through String database to analyze protein-protein interaction,The possible mechanism of Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out by using David platform.Different doses of Naringin(50 mg/kg/d,100 mg/kg/d,200 mg/kg/d)were administered by gavage for 7 days;HE staining was used to observe the pathological morphology and inflammatory cell infiltration in the cecum;immunohistochemistry was used to detect the expression of MMP-9 and α-SMA in the cecal adhesions;Sirius red staining was used to detect the collagen deposition in the cecal adhesions;The expressions of TGF-β1 and α-SMA were detected by Western blotting experiment;The level of TGF-β1 in peritoneal fluid was detected by enzyme-linked immunosorbent assay.Result The high-dose group of AFI can significantly inhibit the formation of adhesion in the rat model and reduce the inflammatory reaction in the damaged cecum,and reduce the level of TNF-α in serum,and increase the expression of MMP-9 in the cecal adhesion tissue.Through data mining,naringin was screened,and 24 direct targets were screened,including MMP-9 and TGF-β,TNF-α and so on.The results of in vivo experiments showed that naringin in each dose group could significantly inhibit the formation of adhesion in the rat model,reduce the inflammatory response,and regulate the adhesion in the adherent tissue in a dose-dependent manner.The expression of α-SMA up regulates the expression of MMP-9 and reduces the deposition of collagen.In addition,the middle dose group and high dose group could reduce TGF-β1 in cecal tissue and peritoneal fluid expression.Conclusion AFI can prevent the occurrence of postoperative peritoneal adhesion.Naringin can significantly inhibit the occurrence of postoperative peritoneal adhesion in the rat model by inhibiting inflammation,reducing fibrosis,reducing collagen deposition and accelerating extracellular matrix degradation.Postoperative peritoneal adhesion formation.