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[目的]观察大鼠经α-硫辛酸(α-lipoic acid,ALA)较长期喂养后,对其毒作用特征及所作用的靶器官,并初步确定未观察到有害作用的最大剂量(NOAEL)。[方法]取Sprague-Dawley大鼠96只,按体重随机分成4组,雌雄各半,分别给予实验组动物180、90、45mg/kg的ALA与1%羧甲基纤维素钠(CMC-Na)混悬液,对照组即给予1%CMC-Na。[结果]给予ALA 90d后,180mg/kg ALA组雌性大鼠出现较明显的中毒体征,死亡动物多达5只,谷丙转氨酶及谷草转氨酶与对照组相比升高2倍以上,提示肝细胞损伤;病理组织学同时显示,180mg/kg ALA组部分雌性大鼠的肝脏出现不同程度的病变。染毒第4周开始,90、180mg/kg ALA组雄性大鼠的体重出现明显下降。除此以外,各组雄性大鼠和对照组及45、90mg/kg ALA组雌性大鼠血常规、肝功能、肾功能、脏器系数、病理组织学检查均未见异常。[结论]ALA的可能作用靶器官为雌性大鼠的肝脏。ALA大鼠90d喂养实验的NOAEL雌雄均为90mg/kg。
[Objective] To observe the toxic effects and target organs of rats after long-term feeding of α-lipoic acid (ALA), and initially determine the NOAEL (no toxic effect) . [Methods] Ninety-six Sprague-Dawley rats were randomly divided into 4 groups according to their body weight. The animals were divided into two groups, male and female. ALA and 1% sodium carboxymethyl cellulose (CMC-Na ) Suspension, the control group was given 1% CMC-Na. [Results] After 90 days of administration of ALA, the obvious signs of poisoning were observed in 180 mg / kg ALA female rats, with up to 5 dead animals and alanine aminotransferase and aspartate aminotransferase more than 2 folds higher than that of the control group, suggesting that hepatocytes At the same time, histopathology also showed that the liver of some female rats in 180 mg / kg ALA group had different degrees of lesions. From the 4th week of exposure, the body weight of 90,180 mg / kg ALA group rats decreased significantly. In addition, there were no abnormalities in blood, liver function, renal function, organ coefficient and histopathological examination in male rats and control group and 45 and 90 mg / kg ALA female rats. [Conclusion] The possible target organ of ALA is the liver of female rats. The 90-day NOAEL male and female ALA rats were fed 90mg / kg.