Study On The Protective Effect And Mechanism Of Shenfu Injection On Myocardial Injury In Sepsis

Objective: We screened the effective targets and related pathways of Ginseng Injection for sepsis by the method of network pharmacology,and then explored various mechanisms of action for the treatment of myocardial injury in sepsis,and made the basis for the subsequent research.To investigate the protective effect of ginseng injection on myocardial injury in sepsis through animal validation and cellular experiments and the mechanism study,and then to discover the molecular research mechanism of ginseng injection on myocardial injury in sepsis and to provide the theoretical basis for clinical practice.Methods: Screening of common targets of action and related pathways of ginseng injection and sepsis through a web-based pharmacology database.Animal experiments were conducted to evaluate the pharmacodynamic mechanism of the protective effect of ginseng injection on myocardial injury in sepsis in vivo using a model of sepsis-induced myocardial injury in mice with lipopolysaccharide.The in vitro model of septic myocardial injury was established by using lipopolysaccharide-induced H9c2 cardiomyocytes in cellular experiments to evaluate the pharmacodynamic mechanism of its in vitro effectResults: The network pharmacology approach was used to screen for gene targets common to Ginseng Injection and sepsis,key targets such as PPI,GO enrichment analysis,KEGG pathway enrichment analysis and construction of drug-component-disease-target network maps.In an in vivo model of lipopolysaccharide-induced septic myocardial injury in mice,compared with the blank control group,elevated body weight,individual organ indices,serum lactate dehydrogenase(LDH),malondialdehyde(MDA)and nitric oxide(NO)as well as HE pathology sections and ultramicroscopy could be observed in myocardial cells with inflammatory cell infiltration and significant damage to myocardial mitochondria,and The expression of Drp1,Pink1,MFF and Parkin were elevated,while the expression of Mfn2 protein was decreased.Compared with the model group,mice in the treatment group showed higher body weight,organ indices,serum LDH,MDA and NO, as well as significantly improved myocardial inflammatory cell infiltration and myocardial mitochondria in HE pathological sections and ultramicroscopy.In an in vitro model of lipopolysaccharide-induced H9c2 cardiomyocytes,fluorescent staining-related indexes such as live-dead cell staining,cytoskeletal protein staining,and JC-1 mitochondrial membrane potential were elevated in the model group compared with the blank group.Compared with the model group,the fluorescence-related indexes such as AM/PI staining,cytoskeletal staining and JC-1 mitochondrial membrane potential of H9c2 cardiomyocytes were decreased in the treatment group.Conclusion: In vivo experiments in mice demonstrated the protective effect of ginseng injection on myocardial injury in sepsis,and its mechanism of action may be related to Mfn2,Pink1,Drp1,MFF and Parkin proteins in mitochondrial energy metabolism.The results showed that ginseng injection could improve the physiological function of mitochondria by regulating the changes of NO,LDH and mitochondrial membrane potential,and thus achieve the protective effect.