RESUMEN
The diaphragm, which is crucial for ventilation, is the primary muscle responsible for inspiration. Patients with severe burns who experience diaphragmatic dysfunction have an increased risk of mortality. Unfortunately, there are currently no effective medications available to prevent or treat this condition. The objective of our study is to utilize bioinformatics to identify potential genes and drugs associated with diaphragmatic dysfunction. In this study, text-mining techniques were utilized to identify genes associated with diaphragmatic dysfunction and recovery. Common genes were then analyzed using GO and KEGG pathway analysis, as well as protein-protein interaction network analysis. The obtained hub genes were processed using Cytoscape software, and their expression levels in diaphragmatic dysfunction were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in severe burn rats. Genes that were confirmed were then examined in drug-gene interaction databases to identify potential drugs associated with these genes. Our analysis revealed 96 genes that were common to both the "diaphragm dysfunction" and "functional recovery" text mining concepts. Gene enrichment analysis identified 19 genes representing 10 pathways. qRT-PCR showed a significant increase in expression levels of 13 genes, including CCL2, CCL3, CD4, EGF, HGF, IFNG, IGF1, IL17A, IL6, LEP, PTGS2, TGFB1, and TNF, in samples with diaphragmatic dysfunction. Additionally, we found that a total of 56 drugs targeted 5 potential genes. These findings provide new insights into the development of more effective drugs for treating diaphragmatic dysfunction and also present substantial opportunities for researching new target pharmacology and promoting drugs in the pharmaceutical industry.
Asunto(s)
Minería de Datos , Diafragma , Descubrimiento de Drogas , Ratas , Animales , Quemaduras/tratamiento farmacológico , Biología Computacional , Masculino , Bases de Datos Factuales , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Mapas de Interacción de ProteínasRESUMEN
Postburn hypermetabolism remains an important clinical problem. During this phase, there is a significant loss of diaphragmatic proteins. Better understanding of respiratory muscle dynamics and potential mechanisms affecting respiratory muscle function is necessary for the development of effective therapeutic approaches. Male Wistar rats were subjected to 50% TBSA burns and sham injuries, and respiratory muscle function was assessed with 0, 1, 4, 7, and 14 days postinjury, including pulmonary function, blood gas analysis, transdiaphragmatic pressure, diaphragm ultrasonography, isolated diaphragm contractility, fatigue index, protein oxidative stress content, and ATP levels. Burned rats had significantly reduced inspiratory time, expiratory time, and tidal volume and significantly increased respiratory rate and minute ventilation. At the same time, the isolated diaphragm contractility, specific force during fatigue, and fatigue index were significantly decreased in the burned rats. Pdi, Pdimax, diaphragm thickness, diaphragm thickening fraction, and diaphragm excursion also decreased significantly postburn, whereas the Pdi/Pdimax ratio increased significantly. Finally, the content of protein carbonyls and lactic acid of burned rats was increased, and ATP levels of burned rats were decreased. The present study demonstrates the dynamic changes in diaphragm contractile properties postburn from both in vivo and in vitro perspectives, while cursorily exploring the possibility that protein oxidative stress and reduced ATP production may be the cause of diaphragm dysfunction. This understanding contributes to the development of methods to mitigate the extent of diaphragmatic function loss after severe burns.