基于NF-κB磷酸化探讨交泰丸干预失眠大鼠小胶质细胞活化的机制OA

Objective:To investigate the mechanism by which Jiaotai Pill(JTP)modulate microglial activation in an insomnia rat model.Methods:Male Sprague-Dawley(SD)rats at SPF grade were randomly divided into 5 groups:the control group,the model group,the positive control group,the low-dose JTP group,and the high-dose JTP group,with 10 rats in each group.The insomnia model was established via intraperitoneal injection of para-chlorophenylalanine(PCPA)at 400 mg/kg for 2 consecutive days.Rats in the low-and high-dose JTP groups were administered JTP decoction intragastrically at doses of 3.85 and 7.70 g/kg respectively,while the positive control group received diazepam solution at 2 mg/kg,and other groups were given an equivalent volume of distilled water,all for 7 consecutive days.Pentobarbital sodium synergistic sleep experiment was performed after the fi-nal administration.ELISA was used to measure neurotransmitter levels in brain tissue,including 5-hydroxytryptamine(5-HT),norepinephrine(NE),γ-aminobutyric acid(GABA),glutamate(Glu),and melatonin(MT).Hippocampal morphology was ob-served using H&E staining.Immunofluorescence was employed to assess the expression of ionized calcium-binding adaptor mole-cule 1(IBA-1)and inducible nitric oxide synthase(iNOS)and Western blot was used to detect nuclear factor-κB p65(NF-κB p65)and phosphor-NF-κB p65.Results:Compared to the model group,both low-and high-dose JTP groups showed significantly increased sleep duration,and reduced sleep latency(P<0.05).NE levels were significantly decreased(P<0.01),while MT and 5-HT levels were markedly increased(P<0.01).Neurons in the CA1 and CA3 regions of the hippocampus exhibited more order-ly arrangements.Expression levels of IBA-1 and iNOS were significantly reduced.Phosphorylated p65/p65 levels in brain tissue were notably decreased(P<0.05).Conclusion:JTP can promote sleep,improve hippocampal morphology,regulate neurotrans-mitter levels,and alleviate microglial activation.The neuroprotective effect of JTP may be attributed to the inhibition of the NF-κB signaling pathway,thereby mitigating microglial activation.