To investigate the mechanism of Hydroxysafflor yellow A in the treatment of hyperlipidemia in LDLR-/-mice based on lipid metabolomics
[Objective]To investigate the effect and mechanism of Hydroxysafflor yellow A(HSYA)on lipid metabolism in LDLR-/-mice with hyperlipidemia induced by high-fat diet based on lipid metabolomics.[Methods]Twenty-eight male LDLR-/-mice were divided into control group and high-fat diet group.The control group was fed with normal diet,and the high-fat group was fed with high-fat diet.After 6 weeks,according to the content of LDL-C,the mice were divided into four groups[model group,simvastatin group,low dose HSYA(3.8 mg/kg)and high dose HSYA(7.6 mg/kg)].The drug was administered for 11 weeks,and high-fat diet was given simultaneously during the drug administration.The content of alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)in serum of mice were detected by automatic biochemical instrument,the pathological morphology of liver histology was observed by hematoxylin-eosin staining,and the fat deposition of liver tissues of mice was observed by oil red O staining,and lipids in the serum of LDLR-/-mice were measured by targeted lipidomic technology.[Results]Compared with the control group,the serum content of LDL-C,TC,TG,AST and ALT in the model group were increased(P<0.05).The liver tissue showed infiltration of lipid droplets of different sizes,disorderly arrangement of hepatocytes,and a large number of lipid deposits.Compared with the model group,the serum content of LDL-C,TC,TG,AST and ALT in the HSYA group were decreased(P<0.05),liver steatosis,lipid deposition and other pathological conditions were improved.The results of lipid profiling showed that there were 14 different lipid molecules(VIP>1,P<0.05).Compared with the model group,17 lipid molecules in the HSYA group showed the opposite trend and had differences,Respectively PE(18∶0/18∶1),PE(18∶0/18∶2),PE(18∶0/20∶3),PE(18∶0/20∶4),PE(O-18∶0/18∶1),PE(O-18∶0/20∶4),LPE(18∶1),LPE(20∶4),FFA(22∶4),PI(18∶0/18∶2),PI(16∶0/18∶1),PI(18∶1/18∶1),LPI(18∶0),PG(18∶1/16∶1),PG(18∶1/18∶1),PG(18∶1/18∶2),PA(18∶1/18∶1)(VIP>1,P<0.05).[Conclusion]Using lipidomics technology,this study found that HSYA could play a role in the treatment of hyperlipidemia by regulating lipid metabolism in the serum of hyperlipidemia LDLR-/-mice,and provided a new reference for its clinical application.
Hydroxysafflor yellow Ahyperlipidemialipidomicsmetabolism of lipid