京尼平苷对关节炎大鼠的镇痛作用及机制

The analgsic effect and possible mechanisms of Geniposide on type Ⅱ collagen-induced arthritis in rats

目的:研究京尼平苷对类风湿关节炎大鼠的镇痛作用及其可能的作用机制。方法:通过注射Ⅱ型胶原和弗氏佐剂建立胶原诱导大鼠关节炎(collagen-induced arthritis,CIA)模型,以机械刺激缩足反射阈值(mechanical withdraw threshold,MWT)为痛阈指标,观察免疫后d 18~24连续腹腔注射给予京尼平苷对CIA大鼠机械痛觉的过敏作用;行为学测试结束后,取L4~5段脊髓背角组织,采用免疫荧光组织化学及Westren Blot观察脊髓背角星型胶质细胞标记物GFAP水平的变化情况,酶联免疫吸附法(ELISA)检测致炎细胞因子TNF-α,IL-1β的水平。结果:与模型组相比,京尼平苷(10和100 mg·kg-1)可显著抗CIA大鼠机械痛过敏作用,同时抑制脊髓背角星型胶质细胞标记物GFAP及致炎细胞因子TNF-α,IL-1β的水平。结论:京尼平苷对CIA诱导的类风湿性关节炎大鼠有显著的镇痛作用,该作用与其抑制脊髓背角胶质细胞活化、降低致炎细胞因子水平有关。

Objective： To investigate the analgsic effects of geniposide on collagen-induced arthritis（CIA）rats and its possible mechanisms. Methods： CIA rat was induced by injecting with Chicken type Ⅱ collagen in Freund＇s complete adjuvant and Freund＇s incomplete adjuvant,CIA rats were subjected to treatment with geniposide at 1,10 and 100 mg·kg^-1 from days 18 to 24 after immunization,the analgesic effect of geniposide by measuring mechanical withdraw threshold（MWT）. After behavioral test,the lumbar segments of spinal dorsal were dissected,the spinal dorsal horn glial fibrillary acidic protein（GFAP）,a biomarker of astrocyte activation,were observed by Immunofluorescence staining and Western Blot. The levels of proinflammatory cytokines TNF-α and IL-1β were determined by ELISA. Results： 10 and 100 mg·kg^-1 geniposide significantly reversed CIA-induced mechanical evoked pain,CIA rat displayed an increasement in GFAP is attenuated by geniposide,as well as the levels of proinflammatory cytokines TNF-α and IL-1β. Conclusion： Geniposide displayed a significant analgesic effect on CIA-induced RA rat,the possible mechanisms may involve the inhibition of astrocyte activation and reduce proinflammatory cytokine production in the spinal cord.