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目的:在进一步明确甘遂毒性作用的基础上,从整体上阐明不同剂量醋制甘遂对大鼠的减毒作用。方法:应用核磁共振技术(NMR)和正交-偏最小二乘判别分析(OPLS-DA)方法分析给予大鼠甘遂(7.875、15.75g/kg)和醋制甘遂水提取物(7.875、15.75g/kg)后,大鼠尿液代谢物变化,并结合血浆生化分析和肝、肾组织病理切片HE染色检测,明确醋制甘遂的减毒作用机制。结果:OPLS-DA分析结果显示,甘遂组能够引起大鼠尿液中柠檬酸,琥珀酸,酮戊二酸、肌酸/肌酐含量降低和牛磺酸、甜菜碱、TMAO的含量增加。但7.875 g/kg醋制甘遂组中,仅引起柠檬酸和α-酮戊二酸含量显著降低,而15.75 g/kg醋制甘遂组会导致琥珀酸,柠檬酸和α-酮戊二酸含量显著降低,牛磺酸,甜菜碱和TMAO含量升高。结论:醋制甘遂的减毒作用具有剂量依赖性,是通过干预甘遂毒性生物标志物和下调肝肾毒性传统指标来发挥其减毒作用。
OBJECTIVE: To clarify the attenuated effect of different dosages of Ganoderma lucidum on rats on the basis of further clarifying the toxic effects of Ganoderma lucidum. Methods: The contents of kansui (7.875,15.75g / kg) and the aqueous extract of kampsuchenensis (7.875, 0.75g / kg) were determined by nuclear magnetic resonance (NMR) and orthogonal partial least square discriminant analysis (OPLS-DA) 15.75g / kg), the urinary metabolites of rats were changed, combined with the analysis of plasma biochemical analysis and the HE staining of pathological sections of liver and kidney to determine the attenuated mechanism of Ganoderma lucidum. Results: OPLS-DA analysis showed that the Kansui group could reduce the contents of citrate, succinate, ketoglutarate, creatine / creatinine and increase the contents of taurine, betaine and TMAO in the urine of rats. However, in the 7.875 g / kg vinegar group, only the contents of citric acid and α-ketoglutarate were significantly decreased, while those of 15.75 g / kg vinegar group caused succinate, citric acid and α-keto- Acid content decreased significantly, taurine, betaine and TMAO content increased. CONCLUSION: The attenuated effect of Ganoderma lucidum is dose-dependent. It exerts its attenuating effect by interfering with the biomarkers of KT and decreasing the traditional indicators of liver and kidney toxicity.