Nicotinamide improves early brain injury in rats with subarachnoid hemorrhage by inhibiting TLR4/NF-κB pathway
Objective To investigate the effects of nicotinamide(NA),an inhibitor of poly ADP-ribose polymerase-1(PARP-1),on early brain injury in rats with subarachnoid hemorrhage(SAH)and its possible mechanism.Methods The SAH model was constructed by puncturing the internal carotid artery of rats.The rats were divided into sham group,SAH group and SAH+NA group.After 48 h,the contents of malondialdehyde(MDA)and nicotinamide adenine dinucleotide(NAD+)were detected by enzyme-linked immunosorbent assay(ELISA).Immunofluorescence examined the 8-OHdG expression.The expression of Toll like receptor 4(TLR-4),nuclear transcription factor-κB(NF-κB),interleukin-1 β(IL-1 β),inducible nitric oxide synthase(iNOS),PARP-1,poly(ADP-ribose)(PAR)and apoptosis-inducing factor(AIF)were detected by western Blotting.Cerebral edema and Evans Blue were measured to investigate the effect of NA on the blood-brain barrier.SAH grade and neurological score were used to investigate the effect of NA on brain injury.Results After SAH for 48 h,the expression of MDA and 8-OHdG increased,while the content of NAD+decreased.NA could inhibit the changes.NA could inhibit the protein expression of PARP-1,PAR and AIF induced by SAH.The expression of TLR4,NF-κB,IL-1 β and iNOS could be significantly decreased by NA.NA could reduce brain edema and Evans blue exudation after SAH,and improve neurological score.Conclusion NA may improve early brain injury after SAH by inhibiting the TLR4/NF-κB inflammatory pathway.
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