紫菀的毒性部位及对小鼠的急性肝损伤作用研究

Toxic Fraction of Radix Asteris and its Acute Hepatotoxicity to Mice

目的分离富集紫菀的毒性成分,研究毒性部位的肝脏急性毒性。方法采用柱层析色谱法分离,以小鼠急性毒性为指标,筛选出紫菀的毒性部位,并测定了LD50。小鼠急性肝脏毒性研究方法主要采用的是血清生化指标(ALT,AST,TBIL)检测和肝组织病理切片检查。结果经硅胶柱层析分离富集,得到紫菀的毒性部位Fr2,其LD50为0.052g/kg。与对照组比较,单次给药后,LD0剂量组小鼠血清ALT、AST均有显著升高,TBIL没有显著差异。组织病理学检查结果表明,紫菀毒性部位LD0剂量可引起小鼠肝脏轻度细胞水肿,可见肝细胞点状坏死、肝小叶及汇管区见有炎细胞浸润;LD100剂量下可引起小鼠肝细胞呈不同程度脂肪变性、细胞水肿,可见肝细胞坏死、肝小叶及汇管区均见有炎细胞浸润。结论紫菀毒性部位的LD50为0.052g/kg,单次给药小剂量对小鼠肝脏有轻微损伤,大剂量可引起小鼠较为严重的急性肝损伤并致死。

Objective The ethyl acetate （ EtOAc） part of 90% ethanol extract of Radix Asteris （ RA） showed strong toxic effect （ LD50 0. 19 g/kg） to mice in our previous investigation. This paper aimed to obtain a refined toxic part from the EtOAc part,and to investigate the acute hepatotoxicity of this toxic part to mice. Methods The toxic part was searched by comparing the toxicity of the combined fractions through the gel silica column chromatography using the death of mice as index. LD50 of the toxic part was determined. The acute hepatotoxicity of the toxic part to mice was measured by biochemical indicators （ ALT,AST and TBIL） in serum and histological examination of liver. Results Fr2 fraction obtained from the EtOAc part was confirmed as the toxic part and its LD50 was 0. 052 g / kg. The acute hepatotoxic test of the toxic part in a lower dose （ LD0） showed that ALT,AST were significantly increased but TBIL had no obvious changes as compared to control group. Histological examination showed that a lower dose （ LD0） of Fr2 could induce slight edema and spotty necrosis of liver cell,as well as phlogocyte infiltration; and a higher dose （ LD100） could induce serious liver injury in mice. Conclusion The value of LD50（ 0. 052g/kg） indicate that Fr2 is the refined toxic fraction of RA. The results of biochemical indicator test and histological examination confirmed the acute hepatotoxicity of Fr2 which induced more serious liver injury to mice given a higher dose than given a lower dose.