曲克芦丁对佐剂性关节炎大鼠滑膜细胞分泌PGE_2、IL-1β和TNF-α水平的影响

Effects of troxerutin on levels of prostaglandins E2,interleukin-1β and tumor necrosis factor-α secreted by synoviocytes of rats with adjuvant arthritis

目的观察曲克芦丁对佐剂性关节炎大鼠滑膜细胞分泌炎性因子PGE2、IL-1β和TNF-α水平的影响。方法采用大鼠足跖皮内注射弗氏完全佐剂诱发大鼠关节炎模型;在致炎后14 d,分别以曲克芦丁18、36、72 mg/kg灌胃给药8 d,用阿司匹林30 mg/kg作灌胃给药为阳性对照。取上述各组的关节滑膜细胞进行体外培养,用放射性免疫法测定培养滑膜细胞上清液中IL-1β、TNF-α和PGE2的水平。结果与正常组相比,佐剂性关节炎大鼠的对侧和前肢关节明显肿胀,培养滑膜细胞上清液中IL-1β、TNF-α和PGE2的水平也明显增加。用曲克芦丁36、72 mg/kg给药8 d后,可显著降低滑膜细胞培养上清液中过高的PGE2、IL-1β和TNF-α水平。经相关性分析表明,曲克芦丁减轻关节肿胀与其抑制滑膜细胞产生PGE2、IL-1β和TNF-α密切相关,相关系数分别为0.9567、0.9432和0.9258。结论曲克芦丁对佐剂性关节炎具有一定的治疗作用,抑制关节滑膜细胞异常分泌PGE2、IL-1β和TNF-α可能是其发挥治疗作用的重要机制。

Objective To observe the effects of troxerutin on the levels of prostaglandins E2（PGE2）,interleukin-1（IL-1）and tumor necrosis factor-α（TNF-α）secreted by synoviocytes of rats with adjuvant arthritis.Methods Adjuvant arthritis in rats was induced by intradermal injection of Furend＇s complete adjuvant via voix pedis of left hind foot except those in normal group（n=8）.14 d after injection,animals in three treatment groups（n=8） were intragastrically given troxerutin at 18,36 and 72 mg/kg,respectively,and those in positive control group（n=8）were given 30 mg/kg of aspirin.Meanwhile,rats in model group（n=8） and normal group were given same volume of 0.5% sodium carboxymethycellulose.All animals were intragastrically administered for 8 d,and then the arthral synoviocytes in each group were obtained and cultured in vitro.The levels of PGE2,IL-1β and TNF-α in the supernatant of the cell culture solutions were determined by radioimmunoassay.Results Compared with normal group,the joints of right hind leg and forward limb in rats with adjuvant arthritis swelled apparently,and the levels of IL-1β,TNF-α and PGE2 in the supernatant increased obviously.After treatment with 36 and 72 mg/kg troxerutin for 8 d,these exorbitant levels of PGE2,IL-1β and TNF-α decreased significantly.Correlation analysis demonstrated that the swollen degree of rat foot was closely correlated with the levels of PGE2,IL-1β and TNF-α.The coefficient correlation was 0.9567,0.9432 and 0.9258,respectively.Conclusion Troxerutin can exert certain therapeutic effects on adjuvant arthritis.The inhibition of PGE2,IL-1β and TNF-α secreted by arthral synoviocytes maybe an important mechanism for these effects.