| Purpose:Danhong Injection(DHI)was widely used in the clinical treatment of ischemic stroke.In this study,network pharmacology was mainly used to explore the key targets and related mechanisms of ischemia-reperfusion treatment as the theoretical basis for the early stage,the relationship between Danhong injection and key targets and the targets were related to cerebral ischemia-reperfusionf injury,so as to provide theories for Danhong injection to be widely used in clinical.Method:Through online databases TCMID(Traditional medical intervention Datebase),TCMSP(Traditional Chinese Medicine Systems Pharmacology),Salvia and Red flower were searched separatly for components of Danhong injection,the targets of cerebral ischemia-reperfusion were got from OMIM(Online Mendelian Inheritance in Man)and Gene card datebases,the drug-disease targets were screened out.The biological functions and KEGG pathways of DHI were analyzed by Cluego through software Cytoscape.Based on the key targets,the MCAO model of experiments were used to verify and observe the apoptosis,the volume of cerebral infarction,and the expression of VEGF protein.Result:1.65 actived ingredients of Salvia and 22 actived ingredients of red flower were screened.367 potential targets of effective components of red flower and 354 potential targets of effective components of Salvia miltiorrhiza were obtained.2.By combining the database information,161 related targets Salvia and red flower were obtained3.The biological process enrichment analysis of the core target mainly included the regulation of apoptosis,the regulation of PRI miRNA transcription by RNA polymerase ll,the regulation of neuroinflammatory reaction,the activity of caspase and the signal pathway of apoptosis,the regulation of outer mitochondrial membrane,and the regulation of vascular endothelial growth factor.4.KEGG pathway enrichment showed the main pathways were mainly focused on tumor,inflammation,angiogenesis,apoptosis.Non-small cell lung cancer,colorectal cancer,pancreatic cancer and others were included of tumor signal pathway.In addition,HIF-1signal,MAPK signal,PI3K-Akt signal,ErbB signal were the most enriched pathways.5.The results showed that there was no difference in mNSS scores of model group and DHI group at 24 h,48h.Compared with model group,72 h DHI group had significant difference(P<0.05).6.There was no infarction in the sham operation group after 72 h by TTC staining.In the model group,the white area indicated the infarction.Compared with the model group,the white infarcted area of DHI group was smaller,which was statistically significant.(P <0.05).7.HE staining was observed at 72 hours after cerebral ischemia-reperfusion in three groups.In the sham operation group,the cell membrane was normal,evenly distributed,and the cell membrane and nucleus were intact.In the model group,there were obvious abnormal tissue structure,structural disorder,uneven cell distribution,a large number of nuclear translocation and pyknosis and destroied structure.In DHI group,there were also destroied tissue structure,disordered cell structure,uneven cell distribution,nuclear translocation and nuclear pyknosis.However,compared with model group,there were less damage changes inDHI group.It is suggested that DHI can reduce the apoptotic cells in cerebral ischemia-reperfusion area.8.By observing the apoptotic cells 72 hours after cerebral ischemia-reperfusion in the three groups,without positive apoptotic cells were found in the sham operation group.In the model group,there was positive Tunel staining.In DHI group,the Tunel positive staining was less than that in model group(P < 0.05).9.Compared with the sham operated group,the expression of VEGF in DHI group was up-regulated 72 hours after ischemia-reperfusion,and that in DHI group was up-regulated 72 hours after ischemia-reperfusion(P < 0.05).Conclusion:1.The core targets about the protective effects of DHI on Ischemia-reperfusion Injury were Jun,AKT1,RELA,VEGF,MAPK,MAPK8,IL6,ESR,FOS and CYNNB1.2.The biological process enrichments were related to the protective effects of Danhonginjection on Ischemia-reperfusion Injury main in apoptosis regulation,neuroinflammatoryresponse,apoptosis,vascular endothelial growth factor regulation.3.The KEGG enrichments pathway in the protective effects of Danhong injection on Ischemia-reperfusion Injury showed that inflammation,angiogenesis and apoptosis.4.Danhong injection can reduce mNSS scores after cerebral ischemia-reperfusion in rats,reduce the infarct area and apoptotic cells in cerebral ischemia-reperfusion area.5.Danhong injection up-regulates VEGF expression in the infarcted area of ischemic stroke. |
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