1,3-二环己基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯的抗炎镇痛作用

Experimental study of the anti-inflammatory and analgesic effects of diethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate

目的探讨1,3-二环己基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯(ZL-5010)体内、体外的抗炎镇痛活性。方法醋酸所致小鼠扭体反应模型评价镇痛作用;二甲苯致小鼠耳廓肿胀模型和角叉菜胶致大鼠足跖肿胀模型评价抗炎作用。细菌脂多糖(LPS,10μg/mL)刺激小鼠腹腔渗出细胞活化作为体外炎症模型。ELISA法检测白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的含量。结果 ZL-5010经灌胃给药,1次/d,连续3 d,在0.25和0.5 0 mmol/kg的剂量下能减少醋酸所致小鼠的扭体次数,抑制二甲苯所致的小鼠耳廓肿胀,抑制角叉菜胶诱导的大鼠足跖肿胀,均具有统计学意义(P<0.05);ZL-5010体外能抑制LPS诱导的小鼠腹腔渗出细胞产生促炎细胞因子IL-1β和TNF-α,具有统计学意义的最低有效浓度分别为10和20μmol/L(P<0.05)。结论首次发现ZL-5010经动物体内灌胃给药具有抗炎镇痛作用,体外可抑制小鼠腹腔渗出细胞产生促炎细胞因子IL-1β和TNF-α。

Objective To study the anti-inflammatory and analgesic activities of diethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate（ZL-5010） in vivo and in vitro.Methods The analgesic effect of ZL-5010 was evaluated by acetic acid-induced writhing response in mice,and the anti-inflammatory effects was assessed in mice with xylene-induced ear edema and in rats with carrageenan-induced paw edema.Mouse peritoneal exudate cells activated by bacterial lipopolysaccharides（LPS） were used to evaluate the anti-inflammatory effect of ZL-5010 in vitro.The levels of interleukin-1β（IL-1β） and tumor necrosis factor-α（TNF-α） in the cell culture supernatant were measured using enzyme-linked immunosorbent assay（ELISA）.Results At the doses of 0.25 and 0.5 mmol/kg,ZL-5010 administered by gavage once daily for 3 days significantly reduced acetic acid-induced writhing frequency and suppressed xylene-induced ear edema in mice,and alleviated paw edema induced by carrageenan in rats（P0.05）.The agent also inhibited the production of the pro-inflammatory cytokines IL-1β and TNF-α by LPS-induced mouse peritoneal exudate cells in vitro,with the statistically significant minimum effective concentrations of 10 and 20 μmol/L,respectively（P0.05）.Conclusion ZL-5010 administered by gavage has anti-inflammatory and analgesic effects in mice and rats,and in mouse peritoneal exudate cell cultures,the agent also inhibits the production of the pro-inflammatory cytokines IL-1β and TNF-α.