论文部分内容阅读
采用基于气相色谱质谱联用技术(GC-MS/MS)的代谢组学方法,分析雷公藤复方配伍前后对大鼠血浆中内源性代谢物的变化,以期阐明基于“异类相制”中医理论的清络通痹方对雷公藤的配伍减毒机制。通过GC-MS/MS分析获得空白对照组、雷公藤组和清络通痹方组大鼠血浆代谢轮廓,正交偏最小二乘法-判别分析(OPLS-DA)显示3组在得分图上区分明显,清络通痹方组各观测值存在着向正常组移动的趋势,提示了清络通痹方的配伍减毒功效。通过变量重要性投影(VIP)值和单因素方差分析筛选差异性代谢物,发现雷公藤组中生糖氨基酸包括丙氨酸、谷氨酰胺、丝氨酸、脯氨酸等水平显著升高,支链氨基酸缬氨酸和异亮氨基酸水平下降,清络通痹方则能够逆转氨基酸水平的紊乱。进一步的代谢通路分析提示清络通痹方配伍减毒机制可能与谷氨酸和谷氨酰胺代谢,丙氨酸、天冬氨酸和谷氨酸代谢以及甘氨酸、丝氨酸和苏氨酸代谢相关。该研究从代谢的角度,说明了雷公藤肝脏毒性的发生与氨基酸代谢,能量代谢等过程密切相关,而清络通痹方通过改善机体氨基酸水平发挥配伍减毒作用。
Metabolomic methods based on gas chromatography-mass spectrometry (GC-MS / MS) were used to analyze the changes of endogenous metabolites in the rat plasma before and after the compound prescription of Tripterygium wilfordii. Traditional Chinese Medicine Theory Qinglv Tongbi side Tripterygium compatibility attenuated mechanism. The plasma metabolic profiles of rats in the blank control group, Tripterygium wilfordiii group and Qingluotongbi group were obtained by GC-MS / MS analysis. Orthogonal partial least squares analysis (OPLS-DA) showed that the three groups were distinguished on the score chart Obviously, the observed values of Qingluotongbi group have the tendency to move toward the normal group, suggesting the compatibility and attenuation effect of Qingluotongbi group. Through the importance variable projection (VIP) value and single-factor analysis of variance to screen the differential metabolites, we found that the contents of glycogenic amino acids including alanine, glutamine, serine and proline in the triptolide group were significantly increased, Amino acid valine and isoleucine levels decreased, Qingluotongbi can reverse the disorder of amino acid levels. Further metabolic pathway analysis suggested that the mechanism of attenuation and clearance of Qingluotongbi group may be related to glutamate and glutamine metabolism, alanine, aspartate and glutamate metabolism, as well as glycine, serine and threonine metabolism. The study from the metabolic point of view, shows that the occurrence of triptolide liver toxicity and amino acid metabolism, energy metabolism and other processes are closely related to the Qinglintongbi Fang through the body to improve the level of amino acid compatibility play an attenuated role.