辛温中药生姜调节肝脏脂质代谢的分子作用机制OA

Objective To conduct an analysis of the molecular mechanism underlying ginger's regulation of hepatic lipid metabolism,provide experimental evidence and a theoretical basis for clarifying the property-related mechanism of ginger,as well as its rational clinical application and development.Methods The hot-cold plate preference test was employed to observe the thermotaxis behavior and changes in temperature sensitivity of mice after drug administration.LC-MS was used for comprehensive detection of lipid metabolites in mouse liver.Combined with PCA and OPLS-DA,differential metabolites were screened out to identify the affected metabolic pathways.RNA was extracted from mouse liver tissues for transcriptome sequencing and library construction,followed by screening of differentially expressed genes(DEGs)and enrichment analysis.The STRING database was utilized to construct a PPI network,so as to determine the core targets and pathways.An integrated analysis of transcriptomic and lipidomic data was performed to establish an interaction network,thus clarifying the major metabolic pathways and related targets.Results Compared with the control group,the body temperature of the ginger-treated group increased significantly(P＜0.05),and the proportion of residence time in the low-temperature zone of the treated mice was also significantly elevated(P＜0.05).Lipidomic analysis identified 106 differential lipids(VIP＞1,P＜0.05,FC＞1.5 or＜0.667),most of which were unsaturated long-chain lipids.Among these differential lipids,95 were significantly down-regulated and 11 were significantly up-regulated,with down-regulated lipids accounting for more than 80％of the total.Transcriptomic analysis revealed 925 DEGs,including 442 significantly down-regulated genes and 483 significantly up-regulated genes.Integrated multi-omics analysis identified 11 key metabolic pathways,namely glycerophospholipid metabolism,linoleic acid metabolism,alpha-linolenic acid metabolism,arachidonic acid metabolism,thermogenesis,and regulation of lipolysis in adipocytes,etc.The key regulatory genes(P＜0.05)were Cyp2b13,Cyp2b9,Cyp2a4,Cyp2a22,Ptgs1,Atp5e,Fgfr3,Uqcr11 and Sirt6.Conclusion Ginger can promote lipolysis to provide more ATP for cells to support high-energy-consuming processes,thereby reducing lipid accumulation and increasing energy supply.This effect not only characterizes the pungent-warm property of ginger,but also exerts a synergistic multi-target mode of action.By regulating the hepatic metabolic network,ginger indirectly affects systemic lipid homeostasis,inflammatory status and cardiovascular protection,which is associated with its efficacy of"dispelling cold and warming the middle energizer".