基于生物信息学探讨养阴益气活血方对脑缺血后神经、免疫、循环及内分泌系统的影响OA

[Objective]To explore the effects of Yangyin Yiqi Huoxue Recipe on the nervous,immune,circulatory and endocrine systems after cerebral ischemia based on bioinformatics.[Methods]The chemical components and their corresponding target genes of the single herbs in Yangyin Yiqi Huoxue Recipe were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom-Mapping Database of Traditional Chinese Medicine(SymMap).Target genes for cerebral ischemia were searched by using Human Disease Gene Network(DisGeNET)and Online Mendelian Inheritance in Man(OMIM)database.Targets related to the nervous,immune,circulatory and endocrine systems were screened by using the Kyoto Encyclopedia of Genes and Genomes(KEGG).The collected target genes of Yangyin Yiqi Huoxue Recipe were mapped with the target genes of cerebral ischemia to obtain the potential target genes for the treatment of cerebral ischemia by Yangyin Yiqi Huoxue Recipe.The protein interaction analysis of the intersection targets of the four systems was performed by using STRING database,and signaling pathways were screened by using the DAVID database.The core targets of the four systems after cerebral ischemia were selected with maximum clique centrality(MCC)method;the"drug-ingredient-core target-pathway"network was constructed by using Cytoscape 3.9.0 software to screen the key active ingredients of Yangyin Yiqi Huoxue Recipe.Molecular docking of the core ingredients with targets was performed by using AutoDock Tools software.A rat model of cerebral ischemia was established,the brain tissue sections were observed by HE staining,and the relative expression levels of target genes were detected by Real-time PCR.[Results]Forty-six major active ingredients of Yangyin Yiqi Huoxue Recipe were predicted;there were 40,69,51 and 19 targets for the nervous,immune,endocrine and circulatory systems after cerebral ischemia treatment by Yangyin Yiqi Huoxue Recipe;key ingredients affecting the four systems after cerebral ischemia,such as quercetin,kaempferol and alpinetin were predicted;the core targets of the four systems were signal transducer and activator of transcription 3(STAT3),non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 1(MAPK1),etc.Molecular docking showed that rutaecarpine had strong binding affinity with visceral aliphatin(VFN),quercetin with matrix metalloproteinase-9(MMP-9),and evodiamine with MAPK3.Animal experiment indicated that Yangyin Yiqi Huoxue Recipe could alleviate the neurological damage of cerebral ischemia rats and effectively increase the relative mRNA expression of protein kinase B(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3A),v-raf-1 murine leukemia viral oncogene homolog 1(RAF1),SRC,MAPK3,etc.[Conclusion]Yangyin Yiqi Huoxue Recipe exerts anti-inflammatory,antioxidant,anti-apoptotic and neurorestorative effects through modulating the expression of pro-inflammatory and pro-apoptotic factors such as PTGS2,SRC and PIK3CA,etc,thereby influencing the nervous,immune,circulatory and endocrine systems.