Effect of dexmedetomidine on kidney injury in sepsis rats through TLR4/MyD88/NF-κB/iNOS signaling pathway.
Eur Rev Med Pharmacol Sci
; 23(11): 5020-5025, 2019 Jun.
Article
in En
| MEDLINE
| ID: mdl-31210339
ABSTRACT
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 ANDMETHODS:
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-1ß, 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.
Full text:
1
Database:
MEDLINE
Main subject:
Signal Transduction
/
Sepsis
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Dexmedetomidine
/
Acute Kidney Injury
/
Adrenergic alpha-2 Receptor Agonists
Type of study:
Prognostic_studies
Limits:
Animals
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Humans
/
Male
Language:
En
Year:
2019
Type:
Article