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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 investigate the anti-inflammatory and analgesic activity of diethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (ZL-5010) in vitro and in vivo. Methods The writhing reaction model induced by acetic acid was used to evaluate the analgesic effect. The anti-inflammatory effect was evaluated by the auricle swelling model induced by xylene and the rat paw edema induced by carrageenan. Bacterial lipopolysaccharide (LPS, 10 μg / mL) stimulated peritoneal exudate cell activation in mice as an in vitro inflammatory model. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Results After oral administration of ZL-5010 for 1 d / d for 3 d, the number of writhing induced by acetic acid in mice was reduced at doses of 0.25 and 0.5 0 mmol / kg, and xylene-induced mice Ear swelling and inhibition of carrageenan-induced rat paw edema were statistically significant (P <0.05); ZL-5010 in vitro can inhibit LPS-induced mouse peritoneal exudative cells produce pro-inflammatory cytokines IL- 1β, and TNF-α, with statistically significant minimum effective concentrations of 10 and 20 μmol / L, respectively (P <0.05). Conclusions It is the first time that ZL-5010 has anti-inflammatory and analgesic effect by intragastric administration in vivo and inhibits the excretion of proinflammatory cytokines IL-1β and TNF-α in mouse peritoneal cavity in vitro.