Analysis of transcriptome characteristics of UTI therapy for cerebral injury after CA/ROSC based on RNA-seq technique

Objective(s): To study the effects and mechanisms of ulinastatin (UTI) on brain injury caused by cardiac arrest/return of spontaneous circulation (CA/ROSC). Materials and Methods: In this study, modeling of CA/ROSC was set up in ۵۶ Sprague Dawley (SD) rats, which were randomly divided into the model group, UTI (۱۰۰۰۰۰U/kg) treatment group, and control group. Each group then was divided into two subgroups: ۲۴ hr and ۷۲ hr. The survival rates between different groups was observed during two weeks. AimPlex multiplex immunoassays technology was performed to detect the expression of inflammatory cytokines in serum, such as IL-۶ and TNF-α. RNA-sequencing (RNA-seq) transcriptome, Gene Ontology (GO), and Kyoto. Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to investigate the possible mechanism of UTI. Western blot and immunohistochemistry were performed to detect the expression of C-C motif chemokine ligand ۲ (CCl۲) and plasminogen (plg) protein expression.Results: The survival rate of the UTI group was significantly higher than the model group during two weeks. And UTI can significantly reduce the content of IL-۶ and TNF-α in serum. GO and KEGG pathway enrichment analysis revealed that differentially expressed genes mainly belonged to the IL-۱۷ signaling pathway and neuroactive ligand-receptor interaction signaling pathway. Besides, UTI can down-regulate the expression of the CCl۲ inflammatory gene and up-regulate the expression of plg in the brain tissue of CA/ROSC rats. Conclusion: UTI has neuroprotective effects on brain injury after CA/ROSC. And the key mechanisms belong to the regulation of immune-inflammatory response as well as the signaling molecules and interaction. 

Keywords:

Brain Injuries , Cardiopulmonary - Resuscitation , Heart Arrest , RNA-Seq , Urinastatin