毛菊苣水提取物急性毒性及其保肝作用研究

Acute Toxicity Research of Cichorium Glandulosum Aqueous Extracts and It's Protective Effect on Acute Liver Injury Mice

目的探讨毛菊苣水提物的急性毒性,并通过D-氨基半乳糖盐酸盐(D-GaIN)、卡介苗联合脂多糖(BCG+LPS)和异硫氰酸-1-萘酯(ANIT)致小鼠肝损伤实验研究探讨毛菊苣水提物的保肝作用。方法急性毒性试验:将小鼠随机分为给药组和空白对照组,并观察记录14 d内小鼠死亡情况、体质量和摄食量等,14 d后处死并做大体解剖,观察其各主要脏器是否异常。保肝实验:将小鼠分成空白对照组、模型组、阳性对照组(联苯双酯组/护肝片组)及毛菊苣水提物0.13 g·kg^(-1)和0.26 g·kg^(-1)剂量组,采用D-GaIN建立化学性肝损伤模型,BCG+LPS建立免疫性肝损伤模型,ANIT建立小鼠黄疸性肝炎模型,经眼球采血,测定血清中ALT、AST、总胆红素(total bilirubin,TBIL)和直接胆红素(direct bilirubin,DBIL)水平,同时测定肝脏指数,并取肝脏做常规HE切片观察。结果小鼠单次最大给药量为150 g(生药)·kg^(-1)未出现死亡及其他急性毒性反应。保肝实验:在D-GaIN致小鼠化学性肝损伤模型中,毛菌苣水提物0.26 g·kg^(-1)剂量组能显著抑制D-GaIN所致的血清ALT、AST和TBIL活性升高(P<0.05或P<0.01);在免疫性肝损伤模型中毛菊苣水提物各剂量组均可显著抑制BCG+LPS所致的小鼠血清ALT、AST活性升高(P<0.01),但对血清中TBIL的含量未见明显改变。在黄疸性肝炎模型中,毛菊苣水提物0.26 g·kg^(-1)剂量组可显著抑制ANIT所致的小鼠血清ALT、AST、TBIL和DBIL活性升高(P<0.01)。此外毛菊苣水提物0.13 g·kg^(-1)剂量组对小鼠血清中TBIL和DBIL的含量也有显著的抑制作用(P<0.01)。肝脏病理切片结果显示毛菌苣水提物各剂量组对本实验中的3种肝损伤均有明显改善作用。结论毛菊苣水提物以最大剂量150 g(生药)·kg^(-1)给药对小鼠未见明显急性毒性反应,对实验性肝损伤具有较好的保护作用。

OBJECTIVE To detect the acute toxicity of Cichorium glandulosum Boiss.et Huet aqueous extracts（MS）, and to research the protective effect of MS on acute liver injury mice induced by D-GaIN, BCG＋LPS and ANIT. METHODS The mice were randomly divided into the treatment group and the normal group in acute toxicity test. The mortality, changes of the body weigh and feed intake of animals were measured. After 14 d, all mice were killed and grossly anatomized, then the internal organs were observed. Liver-protective experiment： Mice were divided into normal group, model group, positive drug group, the low and high dose groups of MS（0.13, 0.26 g·kg^（-1））. Acute liver injury mice mode1 were induced by D-GaIN, BCG＋LPS and ANIT. Then blood from eyeball was used to examine level of serum ALT, AST, TBIL and DBIL. The 1iver index was determined. And the pathologic section of the 1iver was stained for HE expression. RESULTS Acute toxicity test in mice to the single dose of maximum dose of 150 g·kg^（-1） without death and other acute toxicity reaction. In D-GaIN induced chemical liver injury model, MS significantly reduced D-GaIN induced ALT, AST and TBIL at 0.26 g·kg^（-1）（P〈0.05 or P〈0.01）. In the immune liver injury mode, MS significantly（P〈0.01）reduced BCG＋LPS induced ALT, AST at 0.13 and 0.26 g·kg^（-1）, but had no influence on TBIL. In the model of jaundice induced liver injury, MS significantly reduced ANIT induced ALT, AST, TBIL and DBIL at 0.26 g·kg^（-1）（P〈0.01）. In addition, MS significantly reduced TBIL and DBIL at 0.13 g·kg^（-1）（P〈0.01）. Pathologic examination showed liver injury had significantly improved in each treatment groups. CONCLUSION There are not exist the acute toxicity of MS in treatment mice with maximum dose 150 g·kg^（-1）. And, MS has a protective effect on acute liver injury.