基础研究-1,2,3,6-四氢嘧啶二甲酸二乙酯的抗炎镇痛作用.pdfVIP

2012;32(4) 南方医科大学学报（J South Med Univ ） ·553 · 基础研究 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 张 群，周桂保，雷林生，余传林，陈娜娜 南方医科大学药学院，广东 广州 510515 摘要：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 ， 10 µg/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（P0.05）；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20 µmol/L（P0.05）。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。 关键词：四氢嘧啶衍生物；抗炎；镇痛；促炎细胞因子 中图分类号：R967 文献标志码：A 文章编号：1673-4254（2012）04-0553-04 doi: 10.3969/j.issn. 1673-4254.2012.04.025 /kcms/detail/44.1627.R2023.028.html Experimental study of the anti-inflammatory and analgesic effects of diethyl 1, 3-dicyclohexyl- 1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate ZHANG Qun, ZHOU Guibao, LEI Linsheng, YU Chuanlin, CHEN Nana School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China Abstract: 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 sup