黄腐酚抑制炎症信号缓解大鼠关节炎痛的 机制研究.

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 10 μL 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-1β and 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-1β were increased in the spinal cords of the rats in CFA group（ P<0. 05）. The serum levels of IL-1β and TNF-α were 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-3β activity. Compared with CFA group, Xn administration significantly attenuated serum inflam‐mation in the rats （P<0. 05）, and significantly reduced GSK-3β activity and the expression levels of GFAP, NF-κB and IL-1β （P<0. 05）. CONCLUSION: Xanthohumol inhibits NF-κB/IL-1β inflammatory signaling by blocking GSK-3β, thus alleviating arthritis pain in rats. [ABSTRACT FROM AUTHOR]