四逆汤中甘草减附子之毒的代谢组学研究

基于GC-MS代谢组学方法分析四逆汤和缺甘草四逆汤干预后大鼠血浆中的内源性代谢物变化,研究四逆汤中甘草对附子的减毒作用。18只SD大鼠,随机平均分为正常组、四逆汤组和缺甘草四逆汤组。四逆汤组和缺甘草四逆汤组分别灌胃药液(生药质量浓度为0.8 g·m L~(-1)),剂量为0.02 m L·g~(-1),每日1次,连续7 d;正常组给予等体积的生理盐水。末次给药0.5 h,收集血浆样本,应用GC-MS检测。数据进行多元统计分析,得到14个潜在代谢标志物(指认13个),并对其相对含量及代谢途径进行分析。与缺甘草方组相比,四逆汤组对7个代谢标志物进行了回调。通过对这些代谢标志物的生理功能分析,推测四逆汤中甘草可以通过调节方中附子对糖酵解、脂质代谢、三羧酸循环和部分氨基酸等生物代谢途径的影响减低附子之毒性。

Metabonomics on toxicity reduction of Glycyrrhizae Radix et Rhizoma for Aconiti Lateralis Radix Preparata in Sini Tang

To analyze the endogenous metabolite changes in rat plasma after intervention by Sini Tang and Sini Tang without Glycyrrhizae Radix et Rhizoma based on GC-MS metabonomics technology, and study the toxicity reduction effect of Glycyrrhizae Radix et Rhizoma in Sini Tang on Aconiti Lateralis Radix Preparata. Eighteen SD rats were randomly divided into normal group, Sini Tang group and Sini Tang without Glycyrrhizae Radix et Rhizoma group on average. The rats in Sini Tang group and Sini Tang without Glycyrrhizae Radix et Rhizoma group were treated respectively with physic liquor by intragastric administration at the dose of 0.02 mL·g^-1 (equivalent to 0.8 g·mL^-1 crude drugs) once a day for 7 days. The rats in normal group were given with equal volume of saline solution. The plasma samples were collected from each rat 0.5 h after the last administration for GC-MS detection. The data was used for multivariate statistical analysis to obtain 14 potential metabolic markers(13 of them were identified). Then their relative content and metabolic pathways were analyzed. Compared with Sini Tang without Glycyrrhizae Radix et Rhizoma group, seven metabolic markers of were reduced in Sini Tang group. Analysis on physiological functions of these potential metabolic markers showed that the Glycyrrhizae Radix et Rhizoma in Sini Tang could reduce the toxicity of Aconiti Lateralis Radix Preparata by adjusting the glycolysis, lipid metabolism, citrate cycle and some amino acids metabolism.