Eur Rev Med Pharmacol Sci 2019; 23 (11): 5020-5025

DOI: 10.26355/eurrev_201906_18094

Effect of dexmedetomidine on kidney injury in sepsis rats through TLR4/MyD88/NF-κB/iNOS signaling pathway

Y.-H. Jin, Z.-T. Li, H. Chen, X.-Q. Jiang, Y.-Y. Zhang, F. Wu

Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. 35793407@qq.com


OBJECTIVE: The aim of this study was to investigate the effect of dexmedetomidine (DEX) on kidney injury in sepsis rats through the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-κB (NF-κB)/inducible nitric oxide synthase (iNOS) signaling pathway.
MATERIALS AND METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly divided into three groups, including the control group (n=10), lipopolysaccharide (LPS)-induced acute kidney injury (AKI) group (model group, n=10) and DEX treatment group (DEX group, n=10). The model of sepsis was successfully established in rats. The levels of serum creatinine (Cr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), IL-1β, IL-10 and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). The pathological changes in kidney tissues were detected via hematoxylin-eosin (HE) staining. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS in the kidney were detected via fluorescence quantitative Polymerase Chain Reaction (PCR) and Western blotting, respectively.
RESULTS: Compared with the control group, rats in the model group showed significant kidney injury, markedly increased levels of serum Cr, BUN and pro-inflammatory cytokines, remarkably decreased the level of IL-10 (p<0.05), and significantly increased mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS. In the DEX group, AKI was markedly improved, while the expressions of inflammatory cytokines were remarkably declined. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS decreased significantly.
CONCLUSIONS: DEX has a protective effect on LPS-induced AKI, whose mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB/iNOS pathway.

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To cite this article

Y.-H. Jin, Z.-T. Li, H. Chen, X.-Q. Jiang, Y.-Y. Zhang, F. Wu
Effect of dexmedetomidine on kidney injury in sepsis rats through TLR4/MyD88/NF-κB/iNOS signaling pathway

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 11
Pages: 5020-5025
DOI: 10.26355/eurrev_201906_18094