Effect of Luteolin on MCP-1/CCR2 Signaling Axis in Model Rats with Neuropathic Pain
Objective:To investigate the effect of luteolin on neuroglial activation and immune inflam-mation in model rats with neuropathic pain(NP)by regulating monocyte chemotactic protein-1(MCP-1)/CC chemokine receptor 2(CCR2)signaling axis.Methods:The model rats with NP were constructed by chronic compression injury of sciatic nerve.The rats were divided into model group,sodium ferulate group,and low,medium and high dosage groups of luteolin according to random number table method,with 12 rats in each group,and 12 rats in the same period were selected as sham operation group.Rats in each group were intraperitoneally injected and intragastrically administered with corresponding drugs once a day for 14 consecutive days.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)of rats were measured.The mRNA and protein expressions of glial fibrillary acidic protein(GFAP)and microglia marker ionized calcium adaptor protein 1(Iba-1)in the spinal cord were detected by quantitative real time polymerase chain reaction(qRT-PCR)and immunohistochemistry.The levels of CD4+and CD8+in peripheral blood of rats were detected by flow cytometry.Hematoxylineosin staining(HE staining)was used to observe the pathological injury of spinal cord in rats.The levels of inflammatory factors of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of MCP-1 and CCR2 protein in spinal cord was detected by Western blotting.Results:Compared to the sham operation group,the MWT,TWL,proportion of CD4+T cells,and the ratio of CD4+/CD8+in the model group were decreased,the mRNA and protein expression of Iba-1 and GFAP,the proportion of CD8+T cells,the levels of inflammatory factors of IL-6,IL-1β,TNF-α,and the protein expressions of MCP-1 and CCR2 were increased(P＜0.05).Compared to the model group,the MWT,TWL,proportion of CD4+T cells,and the ratio of CD4+/CD8+in the low,medium,and high dosage groups of luteolin and sodium ferulate group were raised,the mRNA and protein expression of Iba-1 and GFAP,the proportion of CD8+T cells,the levels of inflammatory factors IL-6,IL-1β,TNF-α,and the protein expressions of MCP-1 and CCR2 were reduced,and the effect of luteolin was dose-dependent(P＜0.05).Conclusions:Luteolin has the action of anti-inflammation,immune enhancing,inhibiting glial cell activation,and alleviating NP.Its mechanism may be related to the inhibition of MCP-1/CCR2 signaling axis activation.
万方数据
维普
