【摘要】：試驗(yàn)旨在評價(jià)阿司匹林丁香酚酯(aspirin eugenol ester,AEE)對大鼠的急性毒性,了解AEE毒性特點(diǎn)及可能的毒性靶器官,并全面地分析大鼠的致死原因。試驗(yàn)按照改良寇氏法進(jìn)行,預(yù)試驗(yàn)選取50只大鼠,雌雄各半,分為5組,測定絕對致死量(LD100)和最大非致死量(LD0)。根據(jù)預(yù)試驗(yàn)結(jié)果,將80只健康大鼠,雌雄各半,隨機(jī)平均分為7個(gè)藥物組(劑量分別為2.62、3.25、4.03、5.00、6.20、7.69和9.53g/kg)和1個(gè)對照組(給予0.5%的羧甲基纖維素鈉(CMC-Na)進(jìn)行正式試驗(yàn)。灌胃給藥,觀察并記錄大鼠給藥后的臨床癥狀及體重變化。給藥14d后,統(tǒng)計(jì)各劑量組大鼠的死亡時(shí)間及總死亡數(shù),并計(jì)算AEE的半數(shù)致死量(LD50)及其95%可信限。同時(shí)對死亡大鼠及時(shí)進(jìn)行剖檢,將具有病變的組織用10%的甲醛溶液固定,以進(jìn)行病理學(xué)分析。結(jié)果顯示,AEE對大鼠口服的LD50是5.95g/kg,且LD50的95%可信限為5.30~6.68g/kg。對大鼠的死亡時(shí)間進(jìn)行分析可得出,當(dāng)口服AEE的劑量大于4.03g/kg時(shí),其死亡時(shí)間主要集中在染毒后的48~96h內(nèi)。大鼠染毒后3d內(nèi),體重呈下降趨勢,常規(guī)飼養(yǎng)第5天開始,大鼠體重可逐漸恢復(fù)。病理學(xué)檢查分析發(fā)現(xiàn),AEE的劑量在5.00g/kg以上時(shí),對大鼠的肝臟、腎臟和胃腸道有明顯損傷。根據(jù)外源化學(xué)物急性毒性分級(WHO)可知,AEE為實(shí)際無毒化合物,AEE對大鼠毒性靶器官主要是肝臟、腎臟和胃腸道。
[Abstract]:The aim of the experiment was to evaluate the acute toxicity of aspirin eugenol ester (aspirin eugenol ester,AEE) to rats, to understand the toxicity characteristics and possible target organs of AEE, and to analyze the causes of death in rats. 50 rats, half male and half female, were divided into 5 groups. Absolute lethal dose (LD100) and maximum non-lethal dose (LD0) were measured. According to the results of the pre-test, 80 healthy rats, half male and half female, They were randomly divided into seven drug groups (2.62, 3.25, 4.03, 5.00, 6.20, 7.69 and 9.53g/kg, respectively) and one control group (0.5% sodium carboxymethyl cellulose (CMC-Na) for formal trial. The clinical symptoms and body weight changes of rats were observed and recorded by intragastric administration. After 14 days of administration, the time of death and the total number of deaths of rats in each dose group were counted, and the half lethal dose (LD50) of AEE and its 95% confidence limit were calculated. At the same time, the dead rats were examined in time, and the tissues with pathological changes were fixed with 10% formaldehyde solution for pathological analysis. The results showed that the oral LD50 of AEE to rats was 5.95g / kg, and the 95% confidence limit of LD50 was 5.30g / 6.68g / kg 路kg ~ (- 1). The results showed that when the dose of AEE was greater than that of 4.03g/kg, the time of death was mainly within 48 hours after exposure. The body weight of the rats decreased within 3 days after exposure. From the 5th day of routine feeding, the body weight of the rats could gradually recover. Pathological analysis showed that when the dose of AEE was above 5.00g/kg, the liver, kidney and gastrointestinal tract of rats were obviously damaged. According to the acute toxicity grade (WHO) of exogenous chemicals, AEE is a practical non-toxic compound. The target organs of AEE toxicity to rats are mainly liver, kidney and gastrointestinal tract.
【作者單位】： 中國農(nóng)業(yè)科學(xué)院蘭州畜牧與獸藥研究所農(nóng)業(yè)部獸用藥物創(chuàng)制重點(diǎn)實(shí)驗(yàn)室甘肅省新獸藥工程重點(diǎn)實(shí)驗(yàn)室;
【基金】：國家自然科學(xué)基金(31572573) 中國農(nóng)業(yè)科學(xué)院科技創(chuàng)新工程(CAAS-ASTIP-2014-LIHPS-02)
【分類號】：S859.7

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