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目的测定鼠尾草酸(carnosic acid,CA)经口灌胃Sprague-Dawley(SD)大鼠的半数致死量(LD_(50)),并探讨引起动物急性死亡的可能机制。方法取SD大鼠50只,雌雄各半,采用霍恩氏法随机分组,经口染毒,观察14 d,计算其LD_(50),并对主要脏器进行病理学检查。另取SD大鼠40只,雌雄各半,随机分组,以LD_(50)剂量的CA一次性经口染毒后,分别于0、1、4、8 h采血,检测血清中肝肾功能指标、总超氧化歧化酶(total superoxide dismutase,T-SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-PX)、丙二醛(malondialdehyde,MDA)和α肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的含量;同时处死动物取肝和肺制成组织匀浆测定T-SOD、GSH-PX、MDA含量。结果 CA对雄雌SD大鼠的急性经口LD_(50)为3.16 g·kg~(-1)(95%可信限为1.86～5.38 g·kg~(-1))。光镜下死亡动物肝、肾和肺组织可见明显病理学改变;以3.16 g·kg~(-1)剂量的CA一次性经口染毒后,SD大鼠血清中谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、尿素氮(blood urine nitrogen,BUN)、肌酐(creatinine,Cr)的水平,以及肝组织中T-SOD和肺组织中GSH-PX和MDA含量随时间而发生了显著变化。结论 CA属低毒,其急性毒性损伤的主要器官为肝、肾和肺。
Objective To determine the median lethal dose (LD_ (50)) of oral administration of carnosic acid (CA) to Sprague-Dawley rats and to explore the possible mechanism of acute death. Methods Fifty SD rats were randomly divided into male and female rats. Horn’s method was used to randomize the rats. After oral administration for 14 days, the LD_ (50) was calculated and pathological examination was performed on the main organs. In addition, 40 SD rats were randomly divided into two groups randomly. The animals were randomly divided into groups and were given a single oral dose of LD_ (50) doses of CA. Blood samples were collected at 0, 1, 4, , Total superoxide dismutase (T-SOD), glutathioneperoxidase (GSH-PX), malondialdehyde (MDA) and tumor necrosis factor- α, TNF-α). At the same time, the animals were sacrificed and the tissue homogenate of the liver and lung were taken for the determination of T-SOD, GSH-PX and MDA contents. Results The acute oral LD 50 of male and female SD rats was 3.16 g · kg -1 (95% confidence interval 1.86 ~ 5.38 g · kg -1). The pathological changes were observed in the liver, kidney and lung tissues of the dead animals under light microscope. After a single oral dose of CA at a dose of 3.16 g · kg ~ (-1), alanine aminotransferase (ALT ), Aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr), as well as the contents of T-SOD in liver and GSH-PX and MDA in lung tissue Significant changes have taken place. Conclusion CA is a low toxicity, the main organ damage acute liver, kidney and lung.