广陈皮抗高脂血症的血清代谢组学研究

Serum Metabolomics of Hyperlipidemia Intervened by Citri Reticulatae Chachiensis Pericarpium

目的揭示广陈皮干预高脂血症模型的代谢物靶点,构建广陈皮体内成分与内源性生物标记物的关系网络,阐明广陈皮干预高脂血症大鼠模型的作用机制。方法采用血脂4项血清生化指标评价高脂血症大鼠模型以及广陈皮的干预作用;应用超高效液相色谱-串联四极杆飞行时间质谱(UPLC Q-TOF/MS)技术对广陈皮体外化学成分和口服给药后的血中移行成分进行分析鉴定;运用代谢组学技术分析广陈皮对高脂血症大鼠作用的代谢物靶点;构建入血成分与内源性生物标记物关联的数理模型,发掘广陈皮防治高脂血症潜在的药效物质基础。结果与模型组比较,广陈皮组的体质量、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平明显降低(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平明显升高(P<0.05)。共鉴定出11个入血的化学成分;血清代谢组学分析得到19个高脂血症模型生物标记物,其中1 1个为广陈皮干预后具有回调趋势的代谢物;与模型组比较,有4个代谢物的回调作用差异具有统计学意义(P<0.05,P<0.01)。入血成分中川陈皮素和5-去甲川陈皮素葡萄糖醛酸代谢物与内源性生物标记物具有较高的关联性。结论广陈皮抗高脂血症的作用机制可能与调节鞘脂代谢和甘油脂代谢有关。

Objective Based on the effective treatment of hyperlipidemia rats,this study was to reveal the metabolite targets of Citri reticulatae Chachiensis pericarpium(CRCP)in the treatment of hyperlipidemia,to establish the network between the components of CRCP into blood and endogenous biomarkers,and to discover the effective substances in CRCP.Methods The hyperlipidemia model and the treatment of CRCP were evaluated by measurement of triglycerides(TG),total cholesterol(TC),low-density lipoprotein(LDL) and high-density lipoprotein(HDL).The metabolite targets of CRCP on hyperlipidemia rats were analyzed using metabolomics technology.The chemical constituents of CRCP in vitro and blood components were identified using UPLC Q-TOF/MS technology.A mathematical model associated with constituents absorbed into blood and endogenous biomarkers was constructed using the PCMS method,and the potential therapeutic material basis of the prevention and treatment of hyperlipidemia of CRCP was explored.Results Compared with the model group,the body weight,the levels of TG and LDL-C were decreased(P<0.05),and the HDL was increased(P<0.05).Eleven blood components were identified;and 19 biomarkers were obtained by serum metabolomics analysis,of which,11 were recovered after CRCP intervention,and 4 were significantly different(P<0.05).The correlation between the blood components and endogenous biomarkers showed that the metabolites of Nobiletin and glucuronic acid metabolite of 5-demethylnobiletin were highly correlated.Conclusion CRCP can improve hyperlipidemia by regulating sphingolipid metabolism and glycerophospholipid metabolism.