Mechanism of Electroacupuncture Regulation of HIF-1α/CXCR4/NF-κB and HO-1/SOD Signaling Pathway Interactions in VD Rats to Improve Cognitive Function

Lei HAN , Lin YANG , Jian-bo WANG , Jia-hao ZHANG , Yang LI , Yi QU , Ya-nan XUE , Yue-long TIAN , Jun-chao WANG , Ji-dong LIU

Science Technology and Engineering ›› 2026, Vol. 26 ›› Issue (22) : 9305 -9315.

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Science Technology and Engineering ›› 2026, Vol. 26 ›› Issue (22) : 9305-9315 DOI: 10.12404/j.issn.1671-1815.2601102
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Mechanism of Electroacupuncture Regulation of HIF-1α/CXCR4/NF-κB and HO-1/SOD Signaling Pathway Interactions in VD Rats to Improve Cognitive Function
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Abstract

The effects of electroacupuncture on the HIF-1α/CXCR4/NF-κB and HO-1/SOD pathways in the hippocampal tissue of rats with VD (vascular dementia) were investigated to explore the mechanisms underlying its improvement of cognitive impairment. SPF-grade male SD rats were randomly divided into a sham surgery group, a model group, an electroacupuncture group, and a sham electroacupuncture group. A VD model was established by bilateral common carotid artery ligation (2-VO). Electroacupuncture was administered at the “Baihui” “Zusanli” and “Sanyinjiao” acupoints in the electroacupuncture group for once every 15 minutes, once daily, for 14 days. Shallow needling without electrical stimulation was performed in the sham electroacupuncture group. Only fixation was applied in the sham surgery and model groups. Cognitive memory abilities were assessed by the Morris water maze and Y-maze tests. Hippocampal morphology was observed by HE staining. HIF-1α and CXCR4 mRNA expression were detected by real-time quantitative PCR. HIF-1α and CXCR4 protein levels and the p-NF-κB/NF-κB ratio were detected by Western blot. The mean optical density of TNF-α, IL-6, and IL-1β was measured by immunohistochemistry. The mean fluorescence intensity of HO-1 was measured by immunofluorescence. Levels of MDA(malondialdehyde), SOD(superoxide dismutase), and ROS(reactive oxygen species) were measured by ELISA. ROS accumulation was assessed by a fluorescent probe assay. Compared with the sham surgery group, in the model and sham electroacupuncture groups, escape latency was prolonged, platform crossing frequency was reduced, and spontaneous alternation rate is decreased (P<0.01). Hippocampal neuronal organization is disordered. HIF-1α and CXCR4 mRNA and protein expression and the p-NF-κB/NF-κB ratio are increased (P<0.01). TNF-α, IL-6, and IL-1β expression is increased (P<0.01). HO-1 fluorescence intensity is decreased (P <0.01). MDA levels are elevated (P<0.05), SOD activity is decreased (P<0.01), and ROS levels are increased (P<0.05). Compared with the model group, in the electroacupuncture group, escape latency is shortened, the number of platform crossings is increased, and spontaneous alternation rate is increased (P <0.01). Hippocampal damage is reduced. HIF-1α and CXCR4 expression and the p-NF-κB/NF-κB ratio are decreased (P <0.01). TNF-α, IL-6, and IL-1β expression is decreased (P<0.01). HO-1 fluorescence intensity is increased (P<0.01). MDA is decreased (P<0.05), SOD is increased (P <0.01), and ROS is decreased (P<0.05). Neuroinflammation may be alleviated, antioxidant stress resistance may be enhanced, and hippocampal neuronal damage may be repaired by electroacupuncture at the “Baihui” “Zusanli” and “Sanyinjiao” acupoints through balancing the interaction between the HIF-1α/CXCR4/NF-κB inflammatory pathway and the HO-1/SOD antioxidant pathway, thereby improving cognitive function in VD rats.

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vascular dementia / electroacupuncture / pathway interaction / cognitive function / neuroinflammation / antioxidant stress

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Lei HAN, Lin YANG, Jian-bo WANG, Jia-hao ZHANG, Yang LI, Yi QU, Ya-nan XUE, Yue-long TIAN, Jun-chao WANG, Ji-dong LIU. Mechanism of Electroacupuncture Regulation of HIF-1α/CXCR4/NF-κB and HO-1/SOD Signaling Pathway Interactions in VD Rats to Improve Cognitive Function. Science Technology and Engineering, 2026, 26(22): 9305-9315 DOI:10.12404/j.issn.1671-1815.2601102

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