大黄素对CFA诱导小鼠炎性痛的治疗作用及机制

Therapeutic effect and mechanism of emodin on CFA induced inflammatory pain in mice

目的:研究大黄素(emodin)对弗氏完全佐剂(complete Freund’s adjuvant,CFA)诱发的小鼠炎性疼痛的治疗作用及其可能的分子机制。方法:CFA注射于C57BL/6小鼠右后爪足背侧皮下诱导炎性疼痛模型,并用大黄素溶液腹腔注射进行干预。疼痛阈值通过von Frey试验和热板试验进行评估。RT-qPCR和ELISA测定炎症细胞因子肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-1β和IL-6的表达。Western blot检测背根神经节(dorsal root ganglion,DRG)中瞬时受体电位香草酸1(transient receptor potential vanillic acid 1,TRPV1)和瞬时受体电位香草酸4(transient receptor potential vanillic acid 4,TRPV4)蛋白表达。结果:CFA组小鼠的机械疼痛和热痛阈值显著低于对照组(P <0.05)。大黄素治疗可显著提高CFA诱导的炎性疼痛小鼠的机械疼痛和热痛阈值(P <0.05)。与对照组相比,大黄素干预能够显著降低CFA炎性疼痛小鼠DRG和血清中炎症细胞因子TNF-α、IL-1β、IL-6以及DRG中TRPV1和TRPV4的表达水平(P <0.05)。结论:大黄素可能通过下调DRG和血清中炎症细胞因子TNF-α、IL-1β、IL-6以及DRG中疼痛相关离子通道TRPV1和TRPV4的表达来缓解CFA诱导的炎性疼痛。

Objective:To study the therapeutic effect of emodin on inflammatory pain induced by complete Freund’s adjuvant(CFA)in mice and its possible molecular mechanism. Methods:CFA was injected subcutaneously on the dorsal side of the right hind paw of C57BL/6 to induce an inflammatory pain model,and emodin solution was injected intraperitoneally for intervention. The pain threshold was evaluated by the von Frey test and the hot plate test. qRT-PCR and ELISA measure the expression of inflammatory cytokines tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β) and interleukin-6(IL-6). Western blot was used to detect the expression of transient receptor potential vanillic acid 1(TRPV1) and transient receptor potential vanillic acid 4(TRPV4) in dorsal root ganglion(DRG). Results:The mechanical pain and thermal pain thresholds of mice in the CFA group were significantly lower than those of the control group(P < 0.05). Emodin treatment significantly increased mechanical pain and thermal pain threshold in mice with induced inflammatory pain(P < 0.05). Compared with the control group,emodin intervention can not only significantly reduce the inflammatory cytokines TNF-α,IL-1β and IL-6 in DRG and serum of mice with CFA inflammatory pain,but also reduce the expression levels of TRPV1 and TRPV4 in DRG(P < 0.05). Conclusion:Emodin relieves CFA-induced inflammatory pain by reducing the content of inflammatory cytokines TNF-α,IL-1β and IL-6 in DRG and serum,and down-regulating the expression of painrelated ion channels TRPV1 and TRPV4 in DRG.