1.北京中医药大学中医学院,北京 102401
2.北京中医药大学东直门医院骨伤科,北京 100700
3.北京中医药大学国家中医体质与治未病研究院,北京 102401
4.北京中医药大学第三附属医院治未病中心,北京 100029
陈心怡,女,25岁,硕士研究生。研究方向:血脂异常不同证候的基础研究及分子生物学研究。
陈婧,E-mail:jchen@bucm.edu.cn
收稿:2025-04-11,
纸质出版:2026-02-25
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陈心怡,薛晓琳,叶超,等.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[J].北京中医药,2026,45(2):190-195.
CHEN Xinyi,XUE Xiaolin,YE Chao,et al.Effects of Erchen Decoction on PHGDH methylation and the PHGDH-mediated serine metabolism signaling pathway in mice with dyslipidemia of the phlegm-dampness obstruction syndrome[J]. Beijing Journal of Traditional Chinese Medicine,2026,45(02):190-195.
陈心怡,薛晓琳,叶超,等.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[J].北京中医药,2026,45(2):190-195. DOI: 10.16025/j.1674-1307.2026.02.007.
CHEN Xinyi,XUE Xiaolin,YE Chao,et al.Effects of Erchen Decoction on PHGDH methylation and the PHGDH-mediated serine metabolism signaling pathway in mice with dyslipidemia of the phlegm-dampness obstruction syndrome[J]. Beijing Journal of Traditional Chinese Medicine,2026,45(02):190-195. DOI: 10.16025/j.1674-1307.2026.02.007.
目的
2
观察二陈汤对血脂异常痰浊阻遏证小鼠3-磷酸甘油酸脱氢酶(PHGDH)甲基化及其介导的丝氨酸代谢信号通路的影响。
方法
2
将C57BL/6J小鼠作为正常组,取ApoE基因敲除小鼠20只制备血脂异常痰浊阻遏证模型,取5只制备血脂异常脾肾阳虚证模型。造模成功后,用随机数字表法将ApoE基因敲除小鼠分为模型组、方证相应低剂量组、方证相应中剂量组、方证相应高剂量组、方证不相应组,每组各5只。方证相应低、中、高剂量组分别给予二陈汤4.45、8.90、17.8 g/(kg·d)灌胃;方证不相应组给予二陈汤8.90 g/(kg·d)灌胃;正常组、模型组给予相同体积的生理盐水灌胃。均每天灌胃1次,共4周。用酶联免疫吸附试验(ELISA)检测血清PHGDH水平,甲基化敏感限制性内切酶聚合酶链反应(MSRE-PCR)检测主动脉PHGDH基因甲基化水平,逆转录定量聚合酶链反应(RT-PCR)检测主动脉PHGDH mRNA表达水平,液相色谱-质谱联用(LC-MS)法检测血清丝氨酸代谢通路关键代谢物水平。
结果
2
与正常组比较,模型组小鼠PHGDH基因甲基化水平高,PHGDH mRNA表达、血清PHGDH水平低(
P
<
0.05);与模型组比较,方证相应中剂量组PHGDH基因甲基化水平低,PHGDH mRNA表达、血清PHGDH水平、丝氨酸、苏氨酸水平高(
P
<
0.05);与方证相应中剂量组比较,方证不相应组PHGDH基因甲基化水平高,PHGDH mRNA表达、血清PHGDH水平、丝氨酸、苏氨酸水平低(
P
<
0.05)。
结论
2
二陈汤可抑制血脂异常痰浊阻遏证小鼠主动脉PHGDH基因甲基化,从而提高PHGDH基因表达水平,降低氧化应激,激活丝氨酸代谢通路。
Objective
2
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
2
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 metabol
ism pathway were detected by liquid chromatography-mass spectrometry (LC-MS).
Results
2
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
2
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.
LEI L , ZHAO N , ZHANG L , et al . Gut microbiota is a potential goalkeeper of dyslipidemia [J ] . Front Endocrinol (Lausanne) , 2022 , 13 : 950826 .
杨韬 , 何庆勇 , 钟小雪 , 等 . 基于因子分析探讨1019例血脂异常患者的证候要素与靶标特点 [J ] . 北京中医药大学学报 , 2018 , 41 ( 2 ): 165 - 170 .
陈婧 , 杨惠民 , 叶超 , 等 . 痰浊阻遏证及脾肾阳虚证血脂异常患者椎、基底动脉血流动力学特点及其与ONOO-浓度间的相关性研究 [J ] . 环球中医药 , 2019 , 12 ( 9 ): 1323 - 1328 .
CHEN J , YE C , YANG Z , et al . The correlation between the traditional Chinese medicine (TCM) syndrome and the concentration of adiponectin and peroxynitrite in dyslipidemia patients [J ] . Eur J Integr Med , 2016 , 8 ( 6 ): 973 - 979 .
CHEN J , YE C , HU X , et al . Serum metabolomics model and its metabolic characteristics in patients with different syndromes of dyslipidemia based on nuclear magnetic resonance [J ] . J Pharm Biomed Anal , 2019 , 167 : 100 - 113 .
AMELIO I , CUTRUZZOLÁ F , ANTONOV A , et al . Serine and glycine metabolism in cancer . Trends Biochem Sci , 2014 , 39 ( 4 ): 191 - 198 .
SHU Y , HAO Y , FENG J , et al . Non-canonical phosphoglycerate dehydrogenase activity promotes liver cancer growth via mitochondrial translation and respiratory metabolism [J ] . EMBO J , 2022 , 41 ( 23 ): e111550 .
CHEN J , YE C , YANG Z , et al . Effects of Erchen Decoction on oxidative stress-related cytochrome P450 metabolites of arachidonic acid in dyslipidemic mice with phlegm-dampness retention syndrome: a randomized, controlled trial on the correspondence between prescription and syndrome [J ] . Evid Based Complement Alternat Med , 2022 : 1079803 .
陈靖 , 叶超 , 王铁山 , 等 . 血脂异常痰浊阻遏证和脾肾阳虚证小鼠模型的构建思路及模型质量验证 [J ] . 中华中医药杂志 , 2022 , 37 ( 11 ): 6437 - 6441 .
JANG AY , LIM S , JO SH , et al . New trends in dyslipidemia treatment [J ] . Circ J , 2021 , 85 ( 6 ): 759 - 768 .
GITT AK , LAUTSCH D , FERRIÈRES J , et al . Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: results from the dyslipidemia international study Ⅱ [J ] . Atherosclerosis , 2017 , 266 : 158 .
代爽 , 严祖桢 , 丁宇坤 , 等 . 高血压患者中医证候与合并病的相关性研究 [J ] . 北京中医药 , 2025 , 44 ( 3 ): 307 - 310 .
孙雪松 , 赵岩 , 许国磊 , 等 . 李国勤治痰经验浅析 [J ] . 北京中医药 , 2024 , 43 ( 3 ): 280 - 282 .
CHEN J , YE C , YANG Z , et al . Study on the effect of macrophages on vascular endothelium in mice with different TCM syndromes of dyslipidemia and its biological basis based on RNA-Seq technology [J ] . Front Pharmacol , 2021 , 12 : 665635 .
CHO HM , JUN DY , MABAE , et al . Nucleotide sequence and differential expression of the human 3-phosphoglycerate dehydrogenase gene [J ] . Gene , 2000 , 245 ( 1 ): 193 - 201 .
YOSHINO H , ENOKIDA H , OSAKO Y , et al . Characterization of PHGDH expression in bladder cancer: potential targeting therapy with gemcitabine/cisplatin and the contribution of promoter DNA hypomethylation [J ] . Mol Oncol , 2020 , 14 ( 9 ): 2190 - 2202 .
GUO WB , HUANG ZH , YANG C , et al . Down regulating PHGDH affects the lactate production of sertoli cells in varicocele [J ] . Reprod Biol Endocrinol , 2020 , 18 ( 1 ): 70 .
ZHANG B , ZHENG A , HYDBRING P , et al . PHGDH Defines a Metabolic Subtype in Lung Adenocarcinomas with Poor Prognosis [J ] . Cell Rep , 2017 , 19 ( 11 ): 2289 - 2303 .
崔畅婉 , 孙峥嵘 . 3-磷酸甘油酸脱氢酶促进丝氨酸合成在肿瘤进展中的机制 [J ] . 现代肿瘤医学 , 2021 , 29 ( 5 ): 885 - 888 .
SIM WC , LEE W , SIM H , et al . Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease [J ] . Metabolism , 2020 , 102 : 154000 .
SAMANTA D , PARK Y , ANDRABI SA , et al . Retraction: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis [J ] . Cancer Res , 2024 , 84 ( 17 ): 2926 .
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