阿司匹林丁香酚酯的抗炎作用及其可能的作用机制

目的研究阿司匹林丁香酚酯(AEE)的抗炎作用及其可能的作用机制。方法阿司匹林0.2g.kg-1组、丁香酚0.18 g.kg-1组、AEE 0.18和0.36 g.kg-1组小鼠按体重ig给予相应药物,每天1次,连续3 d。用二甲苯致小鼠耳肿胀模型、小鼠腹腔毛细血管通透性增高模型、角叉菜胶致小鼠足跖肿胀模型及小鼠棉球肉芽肿模型观察AEE的抗炎作用,并测定血清中一氧化氮(NO)和足爪组织中前列腺素E2(PGE2)、丙二醛(MDA)和5-羟色胺(5-HT)的含量。结果二甲苯致小鼠耳肿胀实验,模型组肿胀度为(7.0±1.2)mg,阿司匹林、丁香酚、AEE 0.18和0.36 g.kg-1明显抑制耳肿胀度,肿胀度分别为3.9±1.2,4.7±1.9,3.9±1.9和(3.8±1.1)mg(P<0.05,P<0.01)。小鼠腹腔毛细血管通透性实验结果表明,模型组伊文思蓝的渗出(A590 nm)为0.56±0.11,阿司匹林、丁香酚、AEE 0.18和0.36 g.kg-1组腹腔毛细血管通透性均降低,伊文思蓝的渗出(A590 nm)分别为0.29±0.15,0.34±0.12和0.35±0.18(P<0.05,P<0.01)。小鼠棉球肉芽肿实验结果表明,模型组肉芽肿增生(12.5±2.4)mg,阿司匹林、丁香酚、AEE 0.18和0.36 g.kg-1组明显降低,分别为7.0±2.1,9.0±1.7,9.9±1.4和(8.8±1.8)mg(P<0.01);角叉菜胶致小鼠足跖肿胀实验结果表明,AEE 0.18 g.kg-1显著抑制角叉菜胶致炎小鼠足跖肿胀(P<0.05),降低致炎足组织中PGE2,5-HT和血清NO含量,作用与阿司匹林和丁香酚较强或相当。结论 AEE具有明显的抗炎作用,与阿司匹林和丁香酚作用相当;其抗炎机制可能与抑制炎性介质释放有关。

Anti-inflammatory effects of aspirin eugenol ester and the potential mechanism

OBJECTIVE To investigate anti- inflammation of aspirin eugenol ester (AEE) and its possible mechanism. METHODS Mice were divided into 4 groups such as aspirin 0.2 g·kg^-1, eugenol 0.18 g·kg^-1, AEE 0.18 and 0.36 g·kg^-1 groups and were ig administered with corresponding drug once daily for 3 d. Anti-inflammation of AEE was investigated with xylene induced ear swelling model, acetic acid induced peritoneal capillary permeability increase model, carrageenan induced hind paw edema model, and cotton ball induced granuloma of subcutaneous tissue model. The content of nitric oxide (NO) in serum, prostaglandin E₂ (PGE₂), malondialdehyde (MDA) and 5-hydroxytryptamine (5-HT) in paw were measured. RESULTS In the xylene induced ear swelling test, compared to model control group (7.0±1.2)mg, the ear swelling degree decreased to 3.9±1.2, 4.7±1.9, 3.9±1.9 and (3.8±1.1) mg in aspirin, eugenol, AEE 0.18 and 0.36 g·kg^-1(P<0.05, P<0.01), respectively. Experiment results of abdominal capillary permeability of mouse showed that aspirin, AEE 0.18 and 0.36 g·kg^-1 inhibited coeliac capillary permeability, the Evans blue effusion (A_{590 nm}) was 0.29±0.15, 0.34±0.12 and 0.35± 0.18, respectively(P<0.05, P<0.01); the A_{590 nm} of model control group was 0.56±0.11. In cotton ball induced granuloma of subcutaneous tissue test, the content of granulomas of model control, aspirin, eugenol, AEE 0.18 and 0.36 g·kg^-1 groups was 12.5±2.4, 7.0± 2.1, 9.0±1.7, 9.9±1.4 and (8.8±1.8)mg (P<0.01). The result of carrageenan induced hind paw edema test showed that AEE 0.18 g·kg^-1 lightened the paw swelling and reduced significantly the level of PGE₂ and 5- HT in the inflammatory paw tissue and NO in serum; this anti- inflammatory activity was similar or stronger compared with aspirin and eugenol. CONCLUSION AEE has anti-inflammation effect similar with aspirin and eugenol, and the mechanism may be related with its decrease of the content of PGE₂, 5-HT in the phlogistic tissues and NO in serum.