Mechanism of quercetin alleviating postherpetic neuralgia in rats by inhibiting MIP-1α/CCR1/CCR5 signaling pathway / 天津医药

ABSTRACT

Objective To investigate the impact of quercetin(Que)on postherpetic neuralgia(PHN)and chemokine ligand 3(CCL3,namely MIP-1α)/C-C chemokine receptor 1(CCR1)/C-C chemokine receptor 5(CCR5)signaling pathway in rats.Methods Sixty rats were divided into the control group(Con),the PHN group(model group),the L-Que(30 mg/kg)group,the M-Que(60 mg/kg)group,the H-Que(120 mg/kg)group and the H-Que+pathway activator MIP-1α(120 mg/kg Que+0.4 mg/kg recombinant MIP-1α)group.The mechanical paw withdrawal threshold(PWT)and thermal pain threshold(TWL)of rats were detected in each group.The kit was used to detect adenosine,Adenine ribonucleotide(AMP),adenosine diphosphate(ADP)and tumor necrosis factor in spinal dorsal horn samples-α(TNF-α),and interleukin-1 β(IL-1 β)levels in spinal dorsal horn samples.HE staining was applied to observe the pathological sections of spinal dorsal horn.Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn.Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression.Results In the PHN group,the dorsal horn of the spinal cord was ruptured,the arrangement of nerve bundles was disordered,and inflammatory cell infiltration,edema,and slight atrophy of neurons appeared.Compared with the Con group,the PWT value,adenosine,AMP and ADP levels were obviously decreased in the PHN group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1-positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).After treatment with Que,the disordered arrangement of nerve bundles was improved,the infiltration of inflammatory cells was reduced,and the phenomenon of neuronal atrophy disappeared.Compared with the PHN group,the PWT value,adenosine,AMP and ADP levels were obviously increased in the L-Que group,the M-Que group and the H-Que group(P＜0.05).TWL value,TNF-αand IL-1β levels,the number of Iba1-positive microglia,and MIP-1α,CCR1 and CCR5 protein levels were obviously decreased(P＜0.05).The effect of Que was dose dependent.Compared with the H-Que group,PWT value,adenosine,AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1 positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway,thereby reducing PHN.