当归芍药散加味治疗非酒精性脂肪肝代谢组学研究

Metabolomics Study of Modified Danggui Shaoyao San in the Treatment of Nonalcoholic Fatty Liver Disease

目的应用代谢组学气相色谱质谱法检测单纯性非酒精性脂肪肝肝郁脾虚证大鼠血液中内源性代谢物,探讨当归芍药散加味治疗非酒精性脂肪肝的部分机制。方法将24只雄性SD大鼠随机分为空白对照组、模型组、当归芍药散加味组每组8只。采用高糖高脂饲料、慢性束缚应激刺激、饥饱失常法复制模型,治疗组灌胃30 d后,腹主动脉取血,进行气相色谱质谱技术检测内源性代谢物。结果与空白组比较,模型组可指认出18种代谢产物发生明显变化,当归芍药散加味组寻找出三种差异代谢产物,分别是单棕榈酸甘油酯、碳化二亚胺和草酸。结论模型大鼠经高脂饲养后产生病理性代谢产物,可引起脂质代谢、能量代谢、免疫功能等代谢紊乱,最终导致非酒精性脂肪肝肝郁脾虚证的发生;当归芍药散加味可能是通过调控代谢紊乱的机制来治疗非酒精性脂肪肝。此外,碳化二亚胺等部分物质作用机制尚不明确,尚需进一步探讨研究。

Objective To detect the endogenous metabolites in blood of the rats of nonalcoholic fatty liver disease( NAFLD) of liver stagnation and spleen deficiency pattern with the gas chromatography mass spectrometry( GC- MS) of metabolomics and explore the partial mechanism of the modified danggui shaoyao san in the treatment of NAFLD. Methods Twenty- four male SD rats were randomized into a blank control group,a model group and a modified danggui shaoyao san group,8 rats in each one. High sugar and high fat feed,chronic restrict stress and hunger disturbance method were adopted to duplicate the model. In the treatment group,after 30- day lavage,blood was collected from abdominal aorta and GC- MS was used to detect the endogenous metabolites. Results Compared with the blank group,18 metabolites were identified and changed apparently in the model group. In the modified danggui shaoyao san group,three different metabolites were detected,named monopalmitin,carbodiimine and oxalic acid. Conclusion The high fatty feeding produces pathological metabolites in the rat models and induces the disturbance of lipid metabolism,energy metabolism and immune function and consequently,it causes liver stagnation and spleen deficiency of the disease. The modified danggui shaoyao san treats NAFLD by regulating the disturbed metabolism. Additionally,the effect metabolism of it is not so definite for a part of substances,such as carbodiimide and a further exploration is expected.