基于非靶标血浆代谢组学研究少腹逐瘀汤对血瘀证大鼠的干预作用

Study on the Intervention Effect of Shaofu Zhuyu Decoction on Blood Stasis Syndrome Based upon Non-target Plasma Metabolomics Strategy

目的分析少腹逐瘀汤对血瘀模型大鼠血浆内源性代谢物的调节作用,从代谢组学的视角探究少腹逐瘀汤的治疗机制。方法以冰水浴结合肾上腺素的方法建立大鼠血瘀模型,以GC-MS为检测手段获得血浆代谢轮廓,通过倍数(Fold Change)以及单因素方差分析,确定差异性代谢物。结果最终得到天冬酰胺、谷氨酸、核糖醇、尿嘧啶等8种差异性代谢物。除胱氨酸外,其他差异性代谢物的含量在血瘀大鼠体内显著降低。低剂量的少腹逐瘀汤可显著提高尿嘧啶的水平,并使除3-磷酸甘油酸外的差异性代谢物向正常水平回归;高剂量的少腹逐瘀汤可显著提高天冬酰胺、核糖醇的水平,并使木糖醇、尿嘧啶的水平向正常回归。结论少腹逐瘀汤可能通过调节氨基酸代谢、能量代谢发挥对血瘀证的治疗作用,不同剂量的少腹逐瘀汤对血瘀证导致的代谢物紊乱的调节作用可能是不同的。

OBJECTIVE To explore the therapeutic mechanism of Shaofu Zhuyu decoction（SFZYD）on blood stasis syndrome from the perspective of plasma metabolomics.METHODS A blood stasis syndrome rats model was established by icewater bath in combination with an injection with adrenaline.The plasma metabolomic profile was obtained by gas chromatography coupled with mass spectrometry（GC-MS）.Fold change and one-way analysis of variance（ANOVA）were used to search for potential biomarkers.RESULTS Finally,eight potential biomarkers,such as asparagine,glutamic acid,ribitol and uracil,were obtained.The levels of these potential biomarkers,except that of cystine,were decreased significantly in blood stasis syndrome rats.SFZYD at low dose significantly increased the level of uracil,and reversed other potential biomarkers,except 3-phosphoglycerate,into normal level;SFZYD at high dose significantly adjusted the levels of asparagine and ribitol,and xylitol and uracil showed trend towards the normal levels.CONCLUSION SFZYD shows good therapeutic effect on blood stasis syndrome by regulating the metabolism of amino acids and energy,and different doses of SFZYD may have different regulating effects on the potential biomarkers associated with blood stasis.