Binimetinib ameliorates the severity of septic cardiomyopathy by downregulating inflammatory factors.

Background: Septic cardiomyopathy (SCM) has a worse prognosis with mortality rates of up to 70%. Most existing treatment is useless and no specific drug or treatment has been found in patients with myocardial hypofunction.

Methods: We explored the efficacy of the target drugs (Binimetinib) in SCM model in vivo based on high throughput sequencing and bioinformatics analysis. Firstly, a stable SCM mice model was constructed. Secondly, the hub genes of SCM were clarified by high throughput sequencing and bioinformatics analysis. The related pathways and biological process were revealed by Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis. Thirdly, the target drugs of the hub genes were investigated by network pharmacology analysis. Fourthly, the curative effects and hub genes regulatory effects of Binimetinib were demonstrated by SCM mice model. Finally, the regulatory mechanism of the target drugs on the hub genes were analyzed by molecular docking.

Results: 10 CFU/ml P. aeruginosa daubed in wound could establish a stable SCM mice model. Il-6, Il-1β and Tnf were the hub genes of SCM. Immune system process and inflammatory response were the main biological process. Binimetinib was the target drug of IL-6, IL-1β and TNF-α. JUN and NFKB1 were the transcription factor (TFs) of hub genes and Binimetinib had the lowest binding energy with NFKB1.

Conclusions: A stable SCM model was established by wound P. aeruginosa infection. Tnf, Il-1β, Il-6 were the key genes of SCM. Binimetinib might be a drug for the treatment of SCM by downregulating the hub genes. Its active mechanism might be related to NFKB1.