醋制甘遂减毒的血浆代谢组学研究

Plasma metabonomic changes induced by vinegar-processed Kansui treatment

目的比较甘遂醋制前后引起的大鼠血浆代谢组的变化,探讨甘遂醋制减毒可能的代谢调控机制。方法选取SD大鼠30只,适应1周后随机分为5组:对照组、甘遂低剂量组(7.875g/kg)、甘遂高剂量组(15.75g/kg)、醋制甘遂低剂量组(7.875g/kg)和醋制甘遂高剂量组(15.75g/kg),每组6只,持续给予甘遂和醋制甘遂14d后,分别于给药前、给药14d和停药7d取各组大鼠血浆,后加入重水和PBS缓冲溶液制备血浆检测样品。收集各组血浆样品的1 HNMR谱,运用正交偏最小二乘判别法(orthogonal partial least-squares-discriminant analysis,OPLS-DA)分析。结果与甘遂组相比,醋制甘遂组血浆中脂质、3-羟丁酸盐、葡萄糖是升高的,乳酸、肌酸/肌酸酐是降低的,且醋制甘遂组血浆代谢谱特征更靠近正常组。停药7d后,醋制甘遂组恢复较好。结论甘遂醋制后具有减毒作用,能够调控机体能量代谢、脂肪代谢,降低肝脏和肾脏的毒性损伤。这种基于核磁共振波谱和多变量分析的代谢组学方法能够从整体上阐明甘遂醋制减毒的代谢调控机制。

Objective To clarify the toxicity reducing mechanism of vinegar-processed Kansui by comparing the plasma metabonomic profiles induced by Kansui and vinegar-process Kansui treatments. Methods Totally 30 SD rats were divided into five groups： controls, 7.875 g/kg Kansui, 15.75 g/kg Kansui, 7.875 g/kg vinegar-processed Kansui and 15.75 g/kg vinegar-processed Kansui. The treatments lasted for 2 weeks. The plasma samples were obtained before, immediately after and 7 days after withdrawal of drugs; the 1HNMR spectra of each sample were obtained and analyzed by orthogonal partial least-squares-discriminant analysis （OPLS-DA） method. Results Compared with Kansui groups, vinegar-processed Kansui increased plasma lipids, 3-hydrobutyrate and glucose, and decreased the levels of lactate and creatine/creatinine; furthermore, the spectra profiles of vinegar-processed Kansui groups were closer to those of the control group. Seven days after drug withdrawal, the rats of vinegar-processed Kansui groups recovered better than those in Kansui groups. Conclusion Vinegar-processed Kansui has toxicity-reducing effect; it can regulate the metabolism of energy and fat, and reduce the toxicity to the liver and kidney. Plasma metabonomics study based on 1HNMR spectroscopy and multivariate analysis can be used to explore the toxicity-reducing mechanism of vinegar-processed Kansui.