基于代谢组学和肠道菌群研究褐藻寡糖对脂多糖诱导的何首乌致大鼠肝损伤的影响

Protective effect of alginate oligosaccharide on live injury induced by Polygoni multiflori radix in lipopolysaccharide activated rats based on gut microbiota and metabonomics

目的利用代谢组学和肠道菌群技术研究褐藻寡糖对脂多糖诱导的何首乌致大鼠特异质肝损伤的保护作用。方法SD大鼠随机分为正常组、脂多糖组、何首乌组、褐藻寡糖组、脂多糖+何首乌组、褐藻寡糖+脂多糖+何首乌组,按对应剂量灌胃给药。采用基于1H-NMR和UHPLC-MS的非靶向代谢组学技术及16s rDNA测序技术研究褐藻寡糖对肝损伤大鼠的肝脏代谢物及肠道菌群的影响,并采用多元统计分析的方法,通过变量投影重要性值和t检验结果来筛选差异代谢物,利用MetaboAnalyst 5.0平台分析差异代谢物的代谢通路。结果褐藻寡糖明显减轻何首乌所致的大鼠肝损伤,仅可见轻度炎细胞浸润,散在肝细胞坏死,能显著改变何首乌诱导的肝损伤大鼠肠道菌群和内源性代谢物。结论褐藻寡糖对何首乌联合脂多糖诱导的肝损伤具有保护作用,可能是通过影响肠道菌群进而影响体内一些代谢物发挥保护作用的。

Objective To determine the protective effect of alginate oligosaccharide on Polygoni multiflori radix(PM)-induced idiosyncratic hepatotoxicity based on gut microbiota and metabonomics.Methods Sprague-Dawley rats were randomly divided into a control group,an LPS group,a PM ethanol extraction group(PM),an alginate oligosaccharide group(AOS),an LPS+PM group and an AOS+LPS+PM group.The untargeted metabolomic approach was used to determine the protective effect of AOS on the rat liver.1H-NMR and UHPLC-MS technology,as well as 16s rDNA sequencing technology were used.Multivariate analysis was used to screen differential metabolites.The metabolic pathways of differential metabolites were analyzed by MetaboAnalyst 5.0 platform.Results PM-induced idiosyncratic liver injury was obviously decreased,and the liver pathological injury was reduced after giving alginate oligosaccharide.Conclusion Alginate oligosaccharide can protect against liver damage induced by combined Polygoni multiflori radix with LPS,whose mechanism might be through regulating the gut microbiota imbalance and affecting some endogenous metabolites.