阿司匹林丁香酚酯的高效解热作用及作用机制

目的探讨阿司匹林丁香酚酯(AEE)解热作用及其作用机制。方法采用sc给予Wistar大鼠15%酵母混悬液10 ml.kg-1制备发热模型。体温升高>0.8℃的大鼠按分组分别ig给予阿司匹林0.27g.kg-1、丁香酚0.24 g.kg-1、AEE 0.32,0.48,0.65 g.kg-1观察给药后2 h4,h和6 h后大鼠体温,6 h后采血取脑,应用酶联免疫法(ELISA)测定致热大鼠腹中隔区及血浆中精氨加压素(AVP)的含量和下丘脑中及血浆中环磷酸腺苷(cAMP)的含量。结果与发热模型组2 h和6 h自然降温相比较,ig给予AEE 0.32,0.48和0.65 g.kg-1、阿司匹林0.27 g.kg-1、丁香酚0.24 g.kg-1后2 h,大鼠体温分别降温-1.2±0.28,-1.14±0.35,-2.09±0.45,-2.19±0.32(,-0.94±0.42)℃;6 h后分别降温-1.32±0.34,-1.45±0.41,-2.49±0.49,-1.78±0.51(,-1.21±0.29)℃,差异显著(P<0.05)。比较同组药后6 h与2 h的降温作用发现,阿司匹林解热药效作用下降较快,差异显著(P<0.05);丁香酚药效作用时间较为持久,但无增加或下降差异;AEE0.65 g.kg-1药效快速持久,降温作用增加,差异显著(P<0.05)。药后6 h,AEE0.65g.kg-1解热降温作用明显强于阿司匹林和丁香酚,差异极显著(P<0.01)。发热模型组中下丘脑及血浆中cAMP的含量与腹中隔区、血浆中AVP含量较正常对照组高。与发热模型组相比,AEE 0.32,0.48和0.65g.kg-1组、阿司匹林0.27 g.kg-1组、丁香酚0.24 g.kg-1组中腹中隔区中AVP含量明显下降,而血浆中AVP含量明显升高,下丘脑中cAMP的含量明显降低,血浆中cAMP的含量变化不明。结论 AEE的解热作用药效快速持久,明显优于阿司匹林与丁香酚,其解热机制可能通过改变下丘脑中cAMP的含量和腹中隔区、血浆中AVP含量而发挥作用。

Antipyretic effects and its mechanisms of aspirin eugenol ester

OBJECTIVE To investigate the antipyretic effect of aspirin eugenol ester(AEE) and its mechanism. METHODS A wistar rats′ fever model was set up by sc giving 15% yeast suspension 10 ml·kg^-1 in the back. The rats with temperature rising more than 0.8℃ were ig given aspirin 0.27 g·kg^-1, eugenol 0.24 g·kg^-1, and AEE 0.32, 0.48 and 0.65 g·kg^-1, respectively. Then, their body temperature was measured at 2, 4, 6 h after administration. Arginine vasopressin (AVP) content in the ventral septal area (VSA), cyclic adenosine monophosphate(cAMP) levels of hypothalamus and blood plasma were determined by enzyme linked immunosorbent assay 6 h later. RESULTS The body temperature two hours after administration of AEE 0.32, 0.48 and 0.65 g·kg^-1, aspirin 0.27 g·kg^-1, and eugenol 0.24 g·kg^-1 respectively decreased by (-1.2±0.28), (-1.14±0.35), (-2.09±0.45), (-2.19±0.32), and (-0.94±0.42)℃, and was (-1.32± 0.34), (-1.45±0.41), (-2.49±0.49), (-1.78±0.51), and (-1.21±0.29)℃ 6 h later, which had significant different vs the natural drop of temperature of fever model group for 2 h and 6 h. In the same group, a comparison of the falling temperature 2 h and 6 h after administration revealed that the effects of aspirin began to weaken, and that there was signifcant difference between 2 h and 6 h (P<0.05). The antipyretic effect of eugenol was prolonged, but without significant difference. However, antipyretic effects of AEE 0.65 g·kg^-1 were quick- acting and lasted longer, with significant difference between 2 h and 6 h after administration. Aspirin 0.27 g·kg^-1, eugenol 0.24 g·kg^-1, and AEE 0.32, 0.48 and 0.65 g·kg^-1 reduced the level of cAMP in the hypothalamus of fever rats and increased AVP content in plasma and the VSA of fever rats. The changes in cAMP content in plasma of all medication groups were not obvious. CONCLUSION AEE has a greater antipyretic activity than aspirin and eugenol,which may affect the production of AVP and cAMP in fever rats.