基于血清非靶代谢组学探讨补肾降脂方干预ApoE-/-小鼠动脉粥样硬化的效应机制OA

Objective Based on serum non-target metabolomics,the mechanism of Bushen Jiangzhi Recipe(补肾降脂方)intervening in atherosclerosis(AS)in ApoE-/-mice was investigated.Methods ApoE-/-mice were given a high-fat diet to replicate the AS model,and were randomly divided into model group(M group),Bushen group(BS group),and C57BL/6J mice(same strain and age)were the normal control group(C group)and intervened for 12 weeks.The pathological morphology and lipid accumulation of aortic sinus in mice were respectively stained by HE and oil red O.Ultra-performance liquid chromatogra-phy tandem secondary mass spectrometry(UHPLC-MS/MS)was used to detect the metabolites in mouse serum,and bioinformat-ics analysis was used for the differential metabolites and significant enrichment metabolic pathways.Results The M group had typi-cal AS lesions and lipid accumulation.Compared with that in the M group,the area of AS plaques and red-stained lipids in the BS group was significantly reduced.In the positive ion mode,there was an up-regulation of 47 distinct metabolites and a down-regulation of 36 different metabolites in the M group compared with the C group.In the negative ion mode,there was an increase in the levels of 34 metabolites and a decrease in the levels of 38 metabolites.In comparison to those in the M group,the positive ion mode analysis revealed that 20 metabolites were elevated,while 45 metabolites were reduced in the BS group.In the negative ion mode,12 were up-regulated and 53 were down-regulated.Bushen Jiangzhi Recipe can obviously down-regulated the contents of metabolites,such as osthole,1-hexadecyl-sn-glycero-3-phosphocholine,1-(1 z-octadecenyl)-sn-glycero-3-phosphocholine,cyromazine,lysophosphatidylcholine 18∶2,acetylcholine,salicylaldehyde,phytosphingosine,sucrose,1,2-dio-leoyl-sn-glycero-3-phosphate,daidzein 4′-sulfate,methyl hexadecanoate,2-hydroxyamino-4,6-dinitrotoluene and de-oxythymidine 5′-phosphate(dTMP)and significantly up-regulated the contents of metabolites,for example,1,2-diazatet-raenoyl-sn-glycero-3-phosphocholine,N-stearoylsphinganine,securinine,allantoin,iminodiacetic acid and phosphatidyl-choline 38:6.Conclusion Bushen Jiangzhi Recipe can regulate the contents of sucrose and phytosphingosine,starch/sucrose me-tabolism,galactose metabolism and sphingolipid metabolism,and then effectively intervene in AS.