甘遂-甘草配伍对大鼠肾脏毒性代谢组学的影响  

Effect of Kansui Radix Combining with Glycyrrhizae Radix et Rhizoma in Rat's Kidney by Metabonomics

作　　者：唐冰雯[1] 李俊健[2] 毋福海[2] 宋粉云[2] 

机构地区：[1]广州医科大学卫生职业技术学院,广州510180 [2]广东药学院,广州510006

出　　处：《中国实验方剂学杂志》2015年第9期88-92,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广州医学院青年基金项目(2012A02)

摘　　要：目的:根据传统用药习惯,从代谢组学的角度来验证甘遂-甘草以1∶4比例配比时对大鼠肾脏的减毒作用,并在此基础上初步探讨其减毒作用机制。方法:实验采用SD雄性大鼠,随机分为空白对照组,甘遂组,甘草组和甘遂-甘草1∶4组。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、甘草和甘遂-甘草1∶4配比液后的大鼠肾脏代谢物变化,并结合血浆生化分析和肾脏组织病理切片HE染色检测,明确甘遂-甘草1∶4配伍的减毒作用机制。结果:甘草组极少引起血浆生化指标和病理学改变,同时对大鼠肾脏内源性代谢物的变化不大;甘遂组能引起血浆葡萄糖的升高和肌酸、肌酐的下降,造成肾小管上皮细胞水肿和空泡变性,肾小球个别出现瘀血的现象,同时引起肾脏内源性代谢物如胆碱,磷酸胆碱,苯丙氨酸,谷氨酰胺的减少和异亮氨酸,亮氨酸,缬氨酸,丙氨酸,乙酸,肌酸/肌酐的增加;而甘遂-甘草1∶4组并未出现明显的血浆生化指标改变,仅出现肾小球轻微瘀血及肾小管上皮细胞扩张的现象,同时仅引起胆碱,磷酸胆碱和苯丙氨酸的减少。结论:甘遂-甘草以1∶4配伍存在明显的减毒作用,主要是通过甘遂毒性生物标志物含量的变化和肾脏毒性传统指标的下调来体现其减毒效应。Objective： In this study, we investigated the impact of combining Kansui Radix with Glyeyrrhizae Radix et Rhizoma （1：4） on the kidney in rats. On this basis, the mechanism of the reducing toxicity was also studied. Method： Male Sprague-Dawley （SD） rats were randomly assign to four groups, which were controls, Kansui Radix , Glyeyrrhizae Radix et Rhizoma and Kansui Radix-Glycyrrhizae Radix et Rhizoma （ 1：4）. The kidney extract metabonomie analyses of Kansui Radix , Glyeyrrhizae Radix et Rhizoma and Kansui Radix- Glycyrrhizae Radix et Rhizoma （1：4） was used by NMR and OPLS-DA. Clinical biochemical and histopathological assessments were also performed. Result： All the clinical biochemical, histopathologieal and metabolites results were no significant change in Glycyrrhizae Radix et Rhizoma treated rats. Not only the increased glucose and decreased ereatine/creatinine in plasma, but also the renal tubular epithelial cell swelling and vacuoles degeneration, glomerular blood clot were observed in Kansui Radix treated rats. Besides, decreased choline, phosphoryleholine, phenylalanine and glutamine, increased isoleucine, leucine, alanine, valine, acetic acid, creatine/creatinine was observed in Kansui Radix treated rats. In Kansui Radix-Glycyrrhizae Radix et Rhizoma （1：4） treatment group, there was no significant change in plasma index. The histopathologieal changes was only the glomerular congestion and renal tubular epithelial cells expansion. The variations were only declined of choline,phosphorylcholine and phenylalanine in Kansui Radix. Conclusion： Detoxification of Kansui Radix in kidney by combining with Glycyrrhizae Radix et Rhizoma was obvious. It could be owing to the intervention of the biomarker of Kansui Radix and down regulation of the traditional indicator of kidney lesion.

关 键 词：甘遂 甘草 配伍 代谢组学 核磁共振 

分 类 号：R285.5[医药卫生—中药学]