四氢嘧啶类化合物XD-7006的抗炎活性及其作用机制

Anti-Inflammatory Activity of Tetrahydropyrimidine Derivative XD-7006 and Its Mechanism

目的探讨四氢嘧啶类化合物XD-7006(1,3-二正丁基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯)的抗炎活性及其作用机制。方法采用二甲苯诱导小鼠耳廓肿胀模型及角叉菜胶激发的大鼠足趾肿胀模型,观察化合物XD-7006体内抗炎活性;采用脂多糖(LPS)刺激RAW264. 7巨噬细胞作为体外炎症模型,探讨化合物XD-7006体外对RAW264. 7巨噬细胞分泌炎症相关因子一氧化氮(NO)和前列腺素E_2(PGE_2)的影响;采用免疫印迹(Western Blot)法检测RAW264. 7细胞的诱导型一氧化氮合酶(iNOS)和环氧合酶-2(COX-2)蛋白表达。结果化合物XD-7006在给药剂量为80 mg/kg和40 mg/kg时均能不同程度地抑制二甲苯诱导的小鼠耳廓肿胀和角叉菜胶激发的大鼠足趾肿胀,差异有统计学意义(P <0. 05);化合物XD-7006在给药浓度为40,20,10μmol/L时均能抑制RAW264. 7巨噬细胞NO和PGE_2的分泌,并抑制iNOS和COX-2蛋白的表达。结论经体内外实验证实,化合物XD-7006具有抗炎活性,其抗炎机制是通过抑制iNOS和COX-2的酶活性,使炎性相关因子NO和PGE2分泌减少。

Objective To investigate the anti- inflammatory activity of tetrahydropyrimidine derivative XD- 7006（1, 3- dihutyl- 1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester） and its mechanism of action. Methods Xylene-induced murine ear swelling and carrageenan-induced rat paw edema were used to evaluate the anti-inflammatory activity of XD-7006 in vivo. RAW264. 7 macrophages activated by lipopolysaccharides（LPS） were used as an in vitro inflammatory models. The efl）ct of tetrahy- dropyrimidine derivative XD- 7006 on the inflammation related factors secreted by RAW264.7 macrophages such as NO and PGE2 were investigated. The expression of iNOS and COX-2 in RAW264. 7 macrophages were detected by Western Blot. Results Tetrahy- dropyrimidine derivative XD- 7006 could inhibit xylene- induced ear edema in mice and carrageenan- induced toe edema in rats at doses of 80 mg/kg and 40 mg/kg, and the difl-rence was statistically significant（ P 〈 0.05）. Tetrahydropyrimidine derivative XD- 7006 could inhibit the secretion of NO and PGE2 and the expression of iNOS and COX- 2 protein in RAW264. 7 macrophages at doses of 40, 20 and 10 /xmol/L. Conclusion Tetrahydropyrimidine derivative XD-7006 has anti- inflammatory activity through in vivo test and in vitro test, its anti-inflammatory mechanism is to reduce the secretion of inflammatory related factors（NO and PGE2） by inhibiting the activity of iNOS and COX-2.