Effects of Electrothermal Acupuncture on the HIF-1α/S1P/S1PR3 Pathway and Macrophage Polarization in Epididymal White Adipose Tissue of Obese Model Mice

GE Xiaobo; LI Yuanyuan; WEI Jiangyan; NIE Limin; YANG Xin; MIAO Quan; WANG Mina; XI Yawei; ZHAO Luopeng; SONG Yine; SUN Xinru; LIU Lu; LI Bin

doi:10.13288/j.11-2166/r.2026.20.013

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Effects of Electrothermal Acupuncture on the HIF-1α/S1P/S1PR3 Pathway and Macrophage Polarization in Epididymal White Adipose Tissue of Obese Model Mice

更新时间：2026-10-10

- Effects of Electrothermal Acupuncture on the HIF-1α/S1P/S1PR3 Pathway and Macrophage Polarization in Epididymal White Adipose Tissue of Obese Model Mice
- Journal of Traditional Chinese Medicine Vol. 67, Issue 20, Pages: 2227-2235(2026)
- 作者机构：
  
  1.北京中医药大学研究生院，北京市朝阳区北三环东路11号，100029
  2.首都医科大学附属北京中医医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2026.20.013
  CLC：
- Received：07 June 2026，
  
  Revised：2026-08-29，
  
  Accepted：17 August 2026，
  
  Published：17 October 2026
- 稿件说明：
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葛肖波,李媛媛,魏江艳等.电热针对肥胖模型小鼠附睾白色脂肪组织HIF-1α/S1P/S1PR3通路及巨噬细胞极化的影响[J].中医杂志,2026,67(20):2227-2235.

GE Xiaobo,LI Yuanyuan,WEI Jiangyan,et al.Effects of Electrothermal Acupuncture on the HIF-1α/S1P/S1PR3 Pathway and Macrophage Polarization in Epididymal White Adipose Tissue of Obese Model Mice[J].Journal of Traditional Chinese Medicine,2026,67(20):2227-2235.
葛肖波,李媛媛,魏江艳等.电热针对肥胖模型小鼠附睾白色脂肪组织HIF-1α/S1P/S1PR3通路及巨噬细胞极化的影响[J].中医杂志,2026,67(20):2227-2235. DOI： 10.13288/j.11-2166/r.2026.20.013.

GE Xiaobo,LI Yuanyuan,WEI Jiangyan,et al.Effects of Electrothermal Acupuncture on the HIF-1α/S1P/S1PR3 Pathway and Macrophage Polarization in Epididymal White Adipose Tissue of Obese Model Mice[J].Journal of Traditional Chinese Medicine,2026,67(20):2227-2235. DOI： 10.13288/j.11-2166/r.2026.20.013.

摘要

目的

基于缺氧诱导因子-1α（HIF-1α）/鞘氨醇-1-磷酸（S1P）/鞘氨醇-1-磷酸受体3（S1PR3）信号通路介导的巨噬细胞极化，探讨电热针对饮食诱导性肥胖模型小鼠的减重效应及其作用机制。

方法

采用高脂饲料持续喂养小鼠8周建立肥胖小鼠模型，将造模成功的20只小鼠随机分为模型组和电热针组各10只，均持续采用高脂饲料喂养至12周；另设正常组小鼠10只予普通饲料持续喂养12周。实验第9周起，电热针组小鼠予“中脘”、双侧“天枢”、双侧“足三里”电热针刺激30 min，电热针仪器电流设置为（40±0.5）mA，恒定温度（40±0.5）℃；正常组和模型组小鼠固定后不针刺，持续30 min。各组均隔日干预1次，共4周。末次干预10 h后测量各组小鼠体质量、腰围、体长，并计算Lee's指数；采用全自动生化分析仪测定空腹血糖（FBG）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、尿素氮（BUN）、肌酐（Cr）水平；ELISA法检测血清瘦素（LEP）、脂联素（ADPN）水平及附睾白色脂肪组织（eWAT）中S1P水平；HE染色评估eWAT组织形态学改变；流式细胞术分析eWAT中巨噬细胞亚型相关指标，包括巨噬细胞总占比、M1型巨噬细胞占比、M2型巨噬细胞占比、M1/M2值；抗体阵列技术筛选并检测模型组与空白组、电热针组与模型组eWAT中差异表达炎症因子水平；Western Blot法和qPCR法分别检测eWAT中HIF-1α、S1PR3蛋白水平和mRNA表达情况。

结果

与正常组比较，模型组小鼠体质量、Lee's指数、腰围、FBG、TC、TG、HDL-C、LDL-C、AST、ALT水平均显著升高，LEP、S1P水平上升，ADPN水平、ADPN/LEP值下降，M1型巨噬细胞占比、M1/M2值显著升高，M2型巨噬细胞占比显著降低，HIF-1α、S1PR3蛋白及其mRNA水平显著上调（

＜0.05或

＜0.01）。电热针组除HDL-C外，上述各指标均较模型组显著改善（

＜0.05或

＜0.01）。差异表达炎症因子结果显示，模型组eWAT中白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）、白细胞介素-12p70（IL-12p70）水平较正常组升高，电热针组eWAT中白细胞介素-17（IL-17）、白细胞介素-5（IL-5）、白细胞介素-6（IL-6）、白细胞介素-23（IL-23）水平较模型组下降（

＜0.05或

＜0.01）。

结论

电热针对肥胖模型小鼠具有减重效应，其机制可能与抑制HIF-1α/S1P/S1PR3信号通路的激活，使巨噬细胞极化从M1型向M2型转变，进而减轻慢性炎症有关。

Abstract

Objective

To investigate the mechanism underlying the weight loss effect of electrothermal acupuncture （ETA） in diet-induced obese （DIO） model mice based on the hypoxia-inducible factor-1α （HIF-1α）/sphingosine-1-phosphate （S1P）sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway-mediated macrophage polarization.

Methods

An obesity mouse model was established by continuously feeding at a high-fat diet （HFD） for 8 weeks. Twenty successfully modeled obese mice were randomly divided into a model group and an electrothermal acupuncture （ETA） group with 10 mice per group， both of which continued to receive the HFD till week 12. Another 10 mice were assigned to the normal group and fed a standard chow diet continuously for 12 weeks. Starting from week 9 of the experiment， mice in the ETA group received electrothermal acupuncture stimulation at Zhongwan （CV12）， bilateral Tianshu （ST25）， and bilateral Zusanli （ST36） for 30 minutes per session， with the instrument current set at （40±0.5）mA and a constant temperature of （40±0.5）℃. Mice in the normal group and the model group were restrained in the same manner for 30 minutes without acupuncture. All interventions were performed once every other day for a total of 4 weeks. Ten hours after the final intervention， the body weight， waist circumference， and body length of mice in each group were measured， and Lee's index was calculated. Serum biochemical analysis was performed to assess fasting blood glucose （FBG）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （Cr）. Serum leptin （LEP） and adiponectin （ADPN） levels， as well as sphingosine-1-phosphate （S1P） levels in epididymal white adipose tissue （eWAT）， were detected by ELISA. Histomorphological changes in eWAT were monitored via HE staining. Flow cytometry was used to analyze macrophage subtype-related indexes in eWAT， including the total proportion of macrophages， the proportion of M1 macrophages， the proportion of M2 macrophages， and the M1/M2 ratio. Antibody array technology was used to determine the levels of differentially expressed inflammatory factors in eWAT between the model and blank groups， as well as between the ETA and model groups. Western blot and qPCR were used to detect the protein and mRNA expression levels of HIF-1α and S1PR3 in the eWAT， respectively.

Results

Compared to the normal group， the model group showed significantly increased body weight， Lee's index， waist circumference， and FBG， TC， TG， HDL-C， LDL-C， AST， and ALT levels， upgraded LEP and S1P levels， decreased ADPN level and ADPN/LEP ratio， elevated proportion of M1 macrophages and the M1/M2 ratio， reduced proportion of M2 macrophages， and upregulated protein and mRNA expression levels of HIF-1α and S1PR3 （

＜0.05 or

＜0.01）. With the exception of HDL-C， all the abovementioned indicators in the ETA group were significantly improved compared to the model group （

＜0.05 or

＜0.01）. Analysis of differentially expressed inflammatory cytokines revea

led that， compared to the normal group， the levels of interleukin-1β （IL-1β）， interferon-γ （IFN-γ）， interleukin-6 （IL-6）， and interleukin-12p70 （IL-12p70） in the eWAT of the model group were elevated； conversely， the levels of interleukin-17 （IL-17）， interleukin-5 （IL-5）， IL-6， and interleukin-23 （IL-23） in the eWAT of the ETA group decreased compared to the model group （

＜0.05 or

＜0.01）.

Conclusion

ETA exerts a weight-reducing effect in obese model mice， and the mechanism may involve inhibition of the HIF-1α/S1P/S1PR3 signaling pathway activation， which shifts macrophage polarization from the M1 to M2 phenotype， thereby alleviating chronic inflammation.

关键词

Keywords

references

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