黄腐酚抑制炎症信号缓解大鼠关节炎痛的机制研究  

Xanthohumol relieves arthritis pain in rats by inhibiting inflammatory signals

作　　者：王钦 谢敏 王柏军 WANG Qin;XIE Min;WANG Bojun(School of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China)

机构地区：[1]湖北科技学院药学院,湖北咸宁437100

出　　处：《中国病理生理杂志》2023年第6期1070-1076,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年基金资助项目(No.81901149);湖北科技学院校级团队项目(No.2020TD02)。

摘　　要：目的:研究黄腐酚(Xn)对大鼠关节炎疼痛的作用及机制。方法:将30只雄性Sprague-Dawley大鼠随机分成3组(每组10只):对照组、关节炎疼痛模型[左后膝关节内注射完全弗氏佐剂(CFA)]组(CFA组)和CFA+Xn(5 mg/kg鞘内注射)组。记录大鼠痛觉行为及运动能力的变化;分子对接分析Xn与糖原合成酶激酶3β(GSK-3β)的作用关系;免疫荧光和Western blot法分析大鼠脊髓组织中GSK-3β的表达及活性、星形胶质细胞激活状态、核因子κB(NF-κB)信号及白细胞介素1β(IL-1β)表达水平;ELISA法检测大鼠血清IL-1β和肿瘤坏死因子α(TNF-α)水平。结果:与对照组相比,CFA注射诱导大鼠自发缩足次数增加,机械痛阈值下降,运动能力受损(P<0.05);脊髓组织中磷酸化GSK-3β、星形胶质细胞标志物胶质细胞原纤维酸性蛋白(GFAP)、NF-κB和IL-1β表达水平均显著升高(P<0.05);血清中IL-1β和TNF-α水平上调。与CFA组相比,Xn鞘内给药减少大鼠自发缩足次数,上调机械痛阈值,增加转棒停留时间和运动距离(P<0.05);分子对接分析显示Xn可抑制GSK-3β活性;Xn给药显著降低脊髓组织磷酸化GSK-3β、GFAP、NF-κB和IL-1β蛋白水平(P<0.05),以及血清中IL-1β和TNF-α水平(P<0.05)。结论:Xn可能通过降低GSK-3β活性抑制炎症信号,从而缓解大鼠关节炎疼痛。AIM:To explore the effect of xanthohumol(Xn)on arthritis pain in rats and its mechanism.METHODS:Sprague-Dawley rats were randomly divided into three groups(10 rats per group):control group,complete Freund's adjuvant(CFA)group,and CFA+Xn group.A CFA mouse model was established through intra-articular injection with 10μL CFA into the left hind knee joint,and Xn(5 mg/kg)was then intrathecally injected into the rats.Pain behavior and motor ability changes in the rats were recorded.Auto-dock was used for analyzing the binding between Xn and glycogen synthase kinase 3β(GSK-3β),while immunofluorescence and Western blot analysis were used for detecting the expression and activity of GSK-3β,astrocyte status,nuclear factor-κB(NF-κB)level,and interleukin-1β(IL-1β)expression in the spinal cord tissue of the rats.ELISA was used for measuring the serum levels of IL-1βand tumor necrosis factor-α(TNF-α).RESULTS:Compared with control group,treatment with CFA increased the number of flinches,decreased the mechanical threshold,and impaired motor ability(P<0.05).The levels of phosphorylated GSK-3β,astrocyte marker glial fibrillary acidic protein(GFAP),NF-κB,and IL-1βwere increased in the spinal cords of the rats in CFA group(P<0.05).The serum levels of IL-1βand TNF-αwere up-regulated in CFA group(P<0.05).Compared with CFA group,intrathecal administration of Xn reduced the number of spontaneous foot contractions,up-regulated mechanical pain threshold,and increased stay time and motor distance of the rotating rod(P<0.05).Molecular docking analysis found Xn to inhibit GSK-3βactivity.Compared with CFA group,Xn administration significantly attenuated serum inflam‐mation in the rats(P<0.05),and significantly reduced GSK-3βactivity and the expression levels of GFAP,NF-κB and IL-1β(P<0.05).CONCLUSION:Xanthohumol inhibits NF-κB/IL-1βinflammatory signaling by blocking GSK-3β,thus alleviating arthritis pain in rats.

关 键 词：关节炎痛 黄腐酚 炎症 糖原合成酶激酶3Β 大鼠 

分 类 号：R593.22[医药卫生—内科学] R363[医药卫生—临床医学]