Improvement of Blood Gas and Myocardial Injury in Rats with Simulated Acute Mountain Sickness by Modified Shengmai(生脉)Formula and Exploration of Its Mechanism
Objective:Based on network pharmacology and animal experiments,this study aimed to explore the pharmacological effects and mecha-nisms of Modified Shengmai(生脉)formula(MSMF)in treating rats with acute mountain sickness(AMS).Methods:Active ingredients and targets of MSMF as well as the targets related to AMS were searched in TCMSP,ETCM,GeneCards,and DisGenet databases.Protein-pro-tein interaction analysis was conducted using the STRING database.Gene ontology(GO)functional enrichment analysis and KEGG pathway enrichment analysis were carried out using the DAVID platform.AMS models were created through simulated high-altitude hypoxia after seven days of drug treatment.Various indicators including blood gas,white blood cell(WBC)counts,inflammation markers,oxidative stress mark-ers,myocardial enzymes,myocardial injury markers,and myocardial mitochondrial enzyme activity were measured.The expressions of the pro-teins of relevant pathways in rat myocardial tissues were also detected using Western blotting.Results:Sixty-two active components were iden-tified in MSMF,including Celabenzine,Aposiopolamine,Frutinone and AInermin.These components were found to interact with 66 common targets related to AMS,with core targets including ESR1,CA2,EGFR,CA1,and MAPK14.GO enrichment analysis showed that in Biological Process(BP),the formula primarily regulated processes like mitogen-activated protein kinase and nitric oxide biosynthetic control.Molecular function(MF)enrichment highlighted functions related to receptor complexes and lysosomes,while Cellular Component(CC)primarily showed steroids and protein phosphatases.KEGG analysis revealed the involvement of signaling pathways such as HIF-1 and AGE-RAGE in the therapeutic effect of MSMF on AMS.Animal experiment results showed that compared with control group,model group had significantly re-duced blood gas indicators(P＜0.05)and significantly elevated indexes of inflammatory factors,myocardial enzyme spectrum,and biomarkers of myocardial injury(P＜0.01).In myocardial tissue,the level of oxidative stress was significant increased and mitochondrial respiratory chain enzyme activity was significantly decreased(P＜0.01).The protein expressions of P53 and HIF-1α were up-regulated and BCL2 expression was down-regulated(P＜0.05).Compared with model group,treatment with MSMF significantly improved blood gas indicator levels(P＜0.05),reduced inflammatory factors and oxidative stress levels,decreased myocardial enzyme spectrum and myocardial injury marker levels(P＜0.01),significantly increased mitochondrial respiratory chain enzyme activity,and lowered protein expression levels of P53 and HIF-1αin myocardial tissue(P＜0.05),with a significant increase in BCL2 protein expression.Conclusion:MSMF improves blood gas parameters,alleviates inflammation and relieves myocardial injury in rats with AMS.The mechanism may be related to the regulation of the P53/HIF-1α/BCL2 pathway.
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