Cardiovascular

[Effect of electroacupuncture on the SIRT1/HIF-1α/Nrf2 signaling pathway of thoracic aorta in ApoE-/- atherosclerotic mice].

TL;DR

EA may regulate lipid metabolism, alleviate oxidative stress injury, promote vascular intimal repair, and delay the progression of AS in ApoE-/- mice through the activation of the SIRT1/HIF-1α/Nrf2 antioxidant signaling pathway.

Key Findings

High-fat-diet-fed ApoE-/- model mice showed increased body weight and dyslipidemia compared with normal-diet C57BL/6J controls.

  • Model group had significantly decreased serum HDL-C (P<0.01) compared with the control group.
  • Model group had increased body weight and serum LDL-C, TC and TG (P<0.01).
  • Design: 10 C57BL/6J controls; 42 male ApoE-/- mice on high-fat diet for 12 weeks, then randomized to model, EA, EA+inhibitor, and agonist groups (10 per group).

Model mice showed impaired antioxidant status and increased lipid peroxidation relative to controls.

  • Serum SOD and GSH-Px were significantly decreased (P<0.01).
  • Serum MDA was significantly increased (P<0.01).
  • Measured by colorimetric assays.

Model mice showed typical atherosclerotic pathology of the thoracic aorta on HE staining.

  • Findings included thickened intima with uneven surface, endothelial proliferation forming plaques, and inflammatory cell infiltration on the plaque surface.
  • The elastic layer structure was damaged and the medial smooth muscle layer was disordered.
  • Localized foam cells and smooth muscle cell proliferation were seen.

In model mice, aortic SIRT1 and Nrf2 were down-regulated and HIF-1α was up-regulated at both protein and mRNA levels.

  • SIRT1 and Nrf2 protein and mRNA were significantly decreased vs control (P<0.01).
  • HIF-1α protein and mRNA were increased (P<0.01).
  • Measured by Western blot and real-time quantitative PCR.

Electroacupuncture and the SIRT1 agonist resveratrol both improved body weight and lipid profile compared with the model group.

  • Both groups had decreased body weight and decreased serum LDL-C, TC and TG (P<0.01).
  • Serum HDL-C was increased (P<0.01, P<0.05).
  • EA used PC6, HT5 and ST36 with 2 Hz/15 Hz sparse-dense wave, 0.3 mA, 20 min, every other day for 8 weeks; resveratrol was 50 mg/kg intragastric.

Electroacupuncture and resveratrol enhanced antioxidant enzyme activity and reduced MDA compared with the model group.

  • Serum SOD and GSH-Px were increased (P<0.01, P<0.05).
  • Serum MDA was decreased (P<0.01).

EA and agonist treatment improved aortic pathology.

  • HE staining showed intact vascular wall, relatively smooth intima, and only a small amount of endothelial cell abscission.
  • The medial smooth muscle layer was regularly arranged with no obvious elastic layer damage.
  • Only a small amount of foam cells and smooth muscle cell proliferation was observed.

EA and agonist treatment up-regulated aortic SIRT1 and Nrf2 and down-regulated HIF-1α compared with the model group.

  • SIRT1 and Nrf2 protein and mRNA were increased (P<0.01, P<0.05).
  • HIF-1α protein and mRNA were decreased (P<0.01).

Adding the SIRT1 inhibitor EX-527 to EA attenuated the benefits of EA on lipids, oxidative stress and body weight.

  • Compared with the EA group, EA+inhibitor had decreased HDL-C, SOD and GSH-Px (P<0.05).
  • Body weight and serum LDL-C, TC, TG and MDA were increased (P<0.05, P<0.01).
  • EX-527 was given intraperitoneally at 10 mg/kg with EA treatment otherwise identical.

The SIRT1 inhibitor reversed EA's protective effects on aortic morphology and pathway expression.

  • HE staining in EA+inhibitor showed damaged vascular wall integrity, intimal thickening and injury, plaques with inflammatory infiltration, disordered smooth muscle layer, and obvious smooth muscle cell proliferation.
  • SIRT1 and Nrf2 protein and mRNA were reduced vs the EA group (P<0.01, P<0.05).
  • HIF-1α protein and mRNA were increased vs the EA group (P<0.01, P<0.05).

What This Means

This study in mice tested whether electroacupuncture, a form of acupuncture using mild electrical current, could slow the development of atherosclerosis (fatty plaque build-up in arteries). Mice genetically prone to atherosclerosis were fed a high-fat diet for 12 weeks, then treated for 8 weeks with electroacupuncture at three acupoints (Neiguan, Tongli, Zusanli), with a SIRT1-activating compound (resveratrol), or with electroacupuncture plus a SIRT1-blocking drug. Compared with untreated model mice, those receiving electroacupuncture or resveratrol had lower body weight, lower LDL cholesterol, total cholesterol and triglycerides, higher HDL cholesterol, and better markers of antioxidant defense. Their aortas showed less damage under the microscope. They also had higher aortic levels of SIRT1 and Nrf2 (proteins linked to antioxidant defense) and lower levels of HIF-1α. When the SIRT1 inhibitor was added to electroacupuncture, these benefits were largely reduced, which suggests that SIRT1 signaling is involved in how electroacupuncture works in this model. This research suggests electroacupuncture may help reduce blood lipids and oxidative stress and protect the artery lining in mice through the SIRT1/HIF-1α/Nrf2 pathway. These are animal findings with 10 mice per group, so they do not show whether the same effects would occur in people.

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Citation

Luo Y, Hu X, Zeng Y, Zhang N. (2026). [Effect of electroacupuncture on the SIRT1/HIF-1&#x3b1;/Nrf2 signaling pathway of thoracic aorta in ApoE-/- atherosclerotic mice].. Zhen ci yan jiu = Acupuncture research. https://doi.org/10.13702/j.1000-0607.20250953