The Mechanism Of Emodin Regulates Sepsis Induced Myocaedial Injury

Objective:To explore the mechanism of emodin regulating myocardial injury in sepsis based on network pharmacology Methods:1.Firstly,the corresponding target proteins of emodin were obtained through TCMSP database,and the related targets of myocardial injury in sepsis were collected from Gene Cards,OMIM and pharm GKB databases,respectively,the protein-protein interaction network was then constructed in the STRING database,followed by GO function enrichment analysis and KEGG pathway function enrichment analysis by using the David Database to construct a compound-target-pathway-disease network map.Meanwhile,To predicted the mechanism of emodin in treating myocardial injury induced by sepsis.2.Myocardial cell H9C2 was used as the research object.The model of myocardial injury was established by adding LPS into the culture medium.There were divided into Control group,LPS group(10 μg/ml)and LPS + Emodin Group(5,10,15 μmol/l).Cell proliferation was detected by CCK8,apoptosis was analyzed by Flow cytometry analysis,ROS content in mitochondria was measured by Mitosox,mitochondrial membrane potential was detected by JC-10,opening of mitochondrial permeability transition pore was detected by Calcein AM,ultrastructure of mitochondria was analyzed by electron microscopy,and protein expression of related signal pathway was detected by Western Blot.Results:1.Network pharmacological analysis showed that there were 21 potential targets of emodin in the treatment of septic cardiomyopathy,including CASP3,BAX,BCL-2,TP53,ILB,MYC,TNF,PTGS2,PPARG.These targets are critical for the regulation of myocardial injury in sepsis.There were 164 pathways related to GO and 16 pathways related to KEGG.PI3K/AKT,MAPK and TNF signaling pathways were closely related to inflammatory reaction and apoptosis.2.In the cell model of myocardial injury induced by LPS,cell proliferation decreased and cardiomyocyte apoptosis increased,mitochondrial ROS increased,mitochondrial membrane potential decreased,and mitochondrial permeability transition pore opened.Destruction of mitochondrial ultrastructure.To some extent,emodin can inhibit the oxidative stress of myocardial cells induced by sepsis,alleviate the dysfunction of mitochondria,and play a role in myocardial protection.3.In the cell model of myocardial injury induced by LPS,the protein expression levels of p-PI3 K,p-AKT,Caspase-3 and Bax were increased in LPS group,while the protein expression levels of BCL-2 were decreased.Emodin could reverse the above effects,especially at 10 μmol/l.Conclusion:Emodin regulates mitochondrial oxidative stress through PI3K/AKT pathway,reduces apoptosis and myocardial injury induced by sepsis.