1,3-二苯基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯抗炎镇痛作用的研究

目的探讨1,3-二苯基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯（LH-2703）体内外的抗炎镇痛活性。方法采用乙酸所致小鼠扭体反应和热板致痛模型评价镇痛作用;二甲苯致小鼠耳郭肿胀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）刺激小鼠腹腔巨噬细胞活化作为体外炎症模型。酶免疫分析法（EIA）检测前列腺素E2（PGE2）的含量,Griess试剂法检测氧化亚氮（NO）的含量。结果LH-2703能减少乙酸所致小鼠的扭体次数,延长热板致痛的痛阈值,抑制二甲苯诱导的小鼠耳郭肿胀和角叉菜胶诱导的大鼠足跖肿胀。体外能抑制LPS诱导的小鼠腹腔巨噬细胞产生炎症因子PGE2和NO,最低有效浓度分别为20、40μmol/L（P〈0.01,P〈0.05）。结论化合物LH-2703具有抗炎镇痛作用,其作用机制可能与抑制炎症因子PGE2和NO有关。

Study of the anti-inflammatory and antinociceptive effect of 1,3-diphenyl-1,2,3,6-tetrahydro-pyrimidine-4,5-dicarboxylic acid diethyl ester

Objective To study the anti-inflammatory and antinociceptive effect of 1,3-diphenyl-1,2,3,6-tetrahydro-pyrimidine-4,5-dicarboxylic acid diethyl ester（LH-2703） in vivo and in vitro.Methods Acetic acid-induced writhing response and hot plate test in mice were used to evaluate antinociceptive effect.Models of xylene-induced mouse ear swelling and carrageenan-induced rat paw edema were applied to assess anti-inflammatory activity.Mouse peritoneal macrophages activated by lipopolysaccharides（LPS） were used as an in vitro inflammatory model.Prostaglandin E2（PGE2） was determined by enzyme immunoassay（EIA） and the amount of nitric oxide（NO） was evaluated by measuring the nitrite content with Griess reagent.Results LH-2703 reduced the acetic acid-induced writhing frequency,increased the pain threshold in hot plate test,inhibited xylene-induced mouse ear swelling and alleviated rat paw edema induced by carrageenan.In vitro studies revealed that LH-2703 inhibited LPS-induced production of PGE2 and NO by mouse macrophages with minimal effective concentrations at 20 and 40 μmol/L,respectively（P0.01,P0.05）.Conclusion The tetrahydropyrimidine derivative,LH-2703,exhibits anti-inflammatory and antinociceptive activities,and inhibition of the inflammatory mediators PGE2 and NO production may be involved in the mechanisms underlying this effect.