二陈汤对血脂异常痰浊阻遏证小鼠PHGDH甲基化及其介导的丝氨酸代谢信号通路的影响OA

Objective To investigate the effects of Erchen Decoction on 3-phosphoglycerate dehydrogenase(PHGDH)methylation and the PHGDH-mediated serine metabolism signaling pathway in mice with dyslipidemia phlegm-dampness obstruction syndrome.Methods C57BL/6J mice were used as the normal group.Twenty ApoE knockout mice were selected using a random number table method to establish a model of dyslipidemia with phlegm-dampness obstruction syndrome,and five ApoE knockout mice were used to establish a model of dyslipidemia with spleen-kidney yang deficiency syndrome.After successful modeling,the ApoE knockout mice were randomly divided into a model group,a prescription-syndrome corresponding low-dose group,a prescription-syndrome corresponding medium-dose group,a prescription-syndrome corresponding high-dose group,and a prescription-syndrome non-corresponding group,with 5 mice in each group.The prescription-syndrome corresponding low-,medium-,and high-dose groups were administered Erchen Decoction by gavage at doses of 4.45,8.90,and 17.8 g/(kg·d),respectively.The prescription-syndrome non-corresponding group received Erchen Decoction at 8.90 g/(kg·d).The normal and model groups were given an equal volume of normal saline by gavage.All groups were treated once daily for 4 weeks.Serum PHGDH levels were measured by enzyme-linked immunosorbent assay(ELISA).The methylation level of the PHGDH gene in aortic tissue was determined by methylation-sensitive restriction endonuclease polymerase chain reaction(MSRE-PCR).The mRNA expression level of PHGDH in aortic tissue was measured by reverse transcription polymerase chain reaction(RT-PCR).Serum levels of key metabolites in the serine metabolism pathway were detected by liquid chromatography-mass spectrometry(LC-MS).Results Compared with the normal group,the model group showed higher methylation levels of the PHGDH gene and lower PHGDH mRNA expression and serum PHGDH levels(P<0.05).Compared with the model group,the prescription-syndrome corresponding medium-dose group showed lower PHGDH gene methylation levels and higher PHGDH mRNA expression,serum PHGDH levels,and levels of serine and threonine(P<0.05).Compared with the prescription-syndrome corresponding medium-dose group,the prescription-syndrome non-corresponding group showed higher PHGDH gene methylation levels and lower PHGDH mRNA expression,serum PHGDH levels,and levels of serine and threonine(P<0.05).Conclusion Erchen Decoction can inhibit PHGDH gene methylation in the aorta of mice with dyslipidemia phlegm-dampness obstruction syndrome,thereby upregulating PHGDH gene expression,reducing oxidative stress,and activating the serine metabolism pathway.