基于代谢组学的六神曲降血脂作用机制研究

Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabol

研究六神曲对高脂血症模型大鼠的治疗作用,并借助非靶向代谢组学探究六神曲降血脂的作用机制。通过给予高脂饲料构建混合型高脂血症模型大鼠,造模成功后分为模型组、普伐他汀钠组(4.4 mg·kg^(-1))、血脂康组(0.1 g·kg^(-1))、六神曲高剂量组(2.4 g·kg^(-1))、六神曲中剂量组(1.2 g·kg^(-1))、六神曲低剂量组(0.6 g·kg^(-1)),给药周期4周,每日1次,空白组和模型组给予等体积超纯水。以血清脂质水平、肝脏苏木精-伊红(hematoxylin-eosin,HE)染色作为考察指标,研究六神曲对混合型高脂血症的干预作用,并通过非靶向代谢组学技术分析六神曲对混合型高脂血症模型大鼠血浆内代谢物变化的影响,而后通过代谢物通路富集,分析六神曲发挥降血脂作用的机制。结果显示,与模型组相比,六神曲尤其是高剂量可显著降低总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-c)含量(P<0.05或P<0.01);肝脏HE染色发现高剂量组脂肪细胞数量有一定程度的减少。通过非靶向代谢组学技术筛选得到的潜在生物标志物有3-磷酸甘油、鞘氨醇、1-磷酸鞘氨醇、脱氧尿苷等,主要涉及鞘脂代谢过程、甘油磷脂代谢过程、甘油酯代谢途径、嘧啶代谢途径共4条可能与脂质代谢相关的代谢通路。该研究为深入探究六神曲降血脂机制提供借鉴,对进一步推广六神曲的临床应用及增加适应症具有重要意义。

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics.The mixed hyperlipidemia model rats were constructed by giving high-fat chow.After successful modeling,the rats were divided into the model group,pravastatin sodium group(4.4 mg·kg^(-1)),lipotropic group(0.1 g·kg^(-1)),high-dose group(2.4 g·kg^(-1)),medium-dose group(1.2 g·kg^(-1)),and lowdose group(0.6 g·kg^(-1))of Massa Medicata Fermentata,and they were administered for four weeks once daily.An equal volume of ultrapure water was given to the blank group and model group.Serum lipid level and liver hematoxylin-eosin(HE)staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia,and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics.The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment.The results showed that compared with the model group,the Massa Medicata Fermentata administration group,especially the high-dose group,could significantly reduce the content of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01),and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent.The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate,sphingomyelin,sphingosine 1-phosphate,and deoxyuridine,which were mainly involved in the sphingolipid metabolism process,glycerophospholipid metabolism process,glycerol ester metabolism pathway,and pyrimidine metabolism pathway,totaling four possible metabolic pathways related to lipid metabolism.This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata,which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.