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目的考察川紫菀水提取物对大鼠的肝毒性,并探讨其肝毒性与水提取物中吡咯里西啶生物碱成分之间的关系。方法采用HPLC法分析川紫菀水提取物中主要吡咯里西啶生物碱成分,并结合文献报道设定水提取物的给药剂量。将水提取物ig给予SD大鼠,通过测定血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性、肝组织中结合吡咯和还原型谷胱甘肽(GSH)水平及观察肝组织病理改变,考察水提取物的肝毒性。结果川紫菀水提取物中主要吡咯里西啶生物碱成分为clivorine(3.94 mg/g)。单次给予水提取物无论剂量高低,ALT和AST均未见明显改变,但肝组织GSH水平显著下降;多次给药时水提取物高剂量组ALT和AST显著升高(P<0.05)。各给药组肝组织中均可检出结合吡咯,其量与给药剂量大小及次数呈正相关。组织病理学观察未见肝组织有明显病变。结论川紫菀水提取物具有潜在的肝毒性,大剂量的毒性尤为明显。Clivorine是水提取物中的主要生物碱成分,可能是川紫菀肝毒性的主要毒效物质。
OBJECTIVE To investigate the hepatotoxicity of water extract of Chuanxiazhuo on rats and to explore the relationship between its hepatotoxicity and the pyrrolizidine alkaloid composition in water extract. Methods The main constituents of pyrrolizidine alkaloids in water extracts of Chuanxiazhuang were analyzed by HPLC, and the dosage of water extract was set according to the literature. The water extract ig was given to SD rats, and the levels of pyrrole and reduced glutathione (GSH) in liver tissue were observed by measuring the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Pathological changes of liver tissue, examine the liver toxicity of water extract. Results The main pyrrolizidine alkaloid in the water extract of Chuanxiazhuo was clivorine (3.94 mg / g). No significant changes were found in ALT and AST, but the level of GSH in liver tissue was significantly decreased in single dose of water extract. The levels of ALT and AST were significantly increased in high dose water extract group (P <0.05). The liver tissue of each administration group can be detected in the combination of pyrrole, its amount and dose size and frequency was positively correlated. No obvious pathological changes of liver tissue were observed in histopathology. Conclusion The water extract of Aster Sinensis has potential hepatotoxicity, and the toxicity of large dose is especially obvious. Clivorine is the main alkaloid component of water extract and may be the main toxic substance of Hepatica hepatica.