OBJECTIVE: The aim of this study was to investigate the effect of long non-coding ribonucleic acid (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) on sepsis-induced brain injury in mice through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).
MATERIALS AND METHODS: The mouse model of sepsis was established by cecal ligation and puncture induction. The relative expression levels of NEAT1 and NF-κB in brain tissues of mice in healthy group and sepsis group were determined via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting, respectively. Subsequently, the expression of NEAT1 was silenced by transfection of small interfering RNAs (siRNAs). Meanwhile, its effect on NF-κB expression was detected. To further explore the effect of sepsis on brain injury, the content of brain water and the expression levels of apoptosis-related proteins, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX), in mice of healthy group, sepsis group, and sepsis + si-NEAT1 group were measured. Furthermore, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect the proliferation and apoptosis of nerve cells.
RESULTS: The relative expression levels of NEAT1 and NF-κB were significantly increased in the brain tissues of septic mice (p<0.01). Si-NEAT1 transfection significantly decreased the expressions of NEAT1 and NF-κB in brain tissues of septic mice (p<0.05). The content of brain water in mice of sepsis group was evidently increased (p<0.05). However, si-NEAT1 treatment remarkably reduced this content (p<0.05). In addition, sepsis markedly decreased the activity of nerve cells (p<0.05). However, si-NEAT1 could significantly increase the activity of nerve cells in septic mice (p<0.05). Moreover, si-NEAT1 notably decreased the expression of BAX (p<0.05), whereas it increased the expression of Bcl-2 (p<0.05). The results of apoptosis detection revealed that sepsis remarkably promoted the apoptosis of mouse nerve cells (p<0.05). In addition, si-NEAT1 transfection could evidently alleviate the apoptosis of nerve cells in septic mice (p<0.05).
CONCLUSIONS: LncRNA NEAT1 promotes brain injury in septic mice by positively regulating NF-κB. However, si-NEAT1 transfection can reduce this injury.
To cite this article
W.-Q. Liu, Y.-J. Wang, Y. Zheng, X. Chen
Effects of long non-coding RNA NEAT1 on sepsis-induced brain injury in mice via NF-κB
Eur Rev Med Pharmacol Sci
Vol. 23 - N. 9