Chen Yinghua, Sun Wei, Sun Zhongren, Zhao Hongxu, Wu Tong, Song Yuanyu, Wang Haoyu, Qin Ruiqi, Su Xiaoqing, Li Junfeng, Miao Yue, Li Xinran, Wu Lin
The Fifth Department of Acupuncture, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
Heilongjiang University of Chinese Medicine, Harbin, China.
Front Neurol. 2025 Sep 2;16:1629474. doi: 10.3389/fneur.2025.1629474. eCollection 2025.
Vascular dementia (VD) is the only preventable form of dementia-related disease. Electroacupuncture (EA) has been shown to provide significant benefits in the treatment of VD. However, the mechanisms through which EA exerts its therapeutic effects remain unclear. Protein lactylation modification (Kla) is a novel type of post-translational modification that has been shown to be involved in various physiological and pathological processes, including inflammation, immunity, and neurodegenerative diseases. This study, utilizing 4D-Fast data-independent acquisition lactylation quantitative proteomics technology, investigated for the first time the effect of EA intervention on protein lactylation in the hippocampal tissue of rats with VD.
Rats were randomly assigned to three groups: sham surgery (sham), model [four-vessel occlusion (4-VO)], and EA (4-VO + EA). A rat model of VD was established using the four-vessel occlusion (4-VO) method. The 4-VO + EA group underwent EA intervention at the "Shencong" (Ex-HN01) and "Fengchi" (GB 20) acupoints for 21 consecutive days. After behavioral testing, we collected rat tissues for lactylation modification proteomics analysis.
The results indicate that EA enhances learning and memory in rats. Based on lactylation modification proteomics analysis, compared to the sham group, 93 lactylation sites on 76 lactylated proteins were upregulated, whereas 29 lactylation sites on 25 lactylated proteins were downregulated in the 4-VO group. Compared to the 4-VO group, 381 lactylation sites on 250 lactylated proteins were upregulated, whereas 18 lactylation sites on 14 lactylated proteins were downregulated in the 4-VO + EA group. Of these, 12 lactylated proteins, including Vdac3 and Pacsin1, exhibited significant differences in lactylation modification levels between the 4-VO and sham groups. The sites of lactylation of these proteins tend to recover after EA intervention. Functional enrichment and clustering analyses revealed that these proteins were primarily associated with pathways, including the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway, and synaptic vesicle cycle. Importantly, we assessed whether the lactylation modification level of Vdac3 was enhanced following EA intervention.
EA improved cognitive dysfunction in VD rats, and its mechanism may be related to the regulation of protein lactylation modifications in the hippocampal tissue. It involves multiple targets and pathways and may be related to the enhanced level of Vdac3 lactylation modification.
血管性痴呆（VD）是唯一可预防的痴呆相关疾病形式。电针（EA）已被证明在VD治疗中具有显著益处。然而，EA发挥其治疗作用的机制仍不清楚。蛋白质乳酰化修饰（Kla）是一种新型的翻译后修饰，已被证明参与各种生理和病理过程，包括炎症、免疫和神经退行性疾病。本研究利用4D-快速数据非依赖采集乳酰化定量蛋白质组学技术，首次研究了EA干预对VD大鼠海马组织中蛋白质乳酰化的影响。
将大鼠随机分为三组：假手术组（sham）、模型组[四血管闭塞（4-VO）]和电针组（4-VO+EA）。采用四血管闭塞（4-VO）法建立VD大鼠模型。4-VO+EA组在“神聪”（Ex-HN01）和“风池”（GB 20）穴位连续进行21天的EA干预。行为测试后，收集大鼠组织进行乳酰化修饰蛋白质组学分析。
结果表明，EA可增强大鼠的学习和记忆能力。基于乳酰化修饰蛋白质组学分析，与假手术组相比，4-VO组中76个乳酰化蛋白上的93个乳酰化位点上调，而25个乳酰化蛋白上的29个乳酰化位点下调。与4-VO组相比，4-VO+EA组中250个乳酰化蛋白上的381个乳酰化位点上调，而14个乳酰化蛋白上的18个乳酰化位点下调。其中，包括Vdac3和Pacsin1在内的12个乳酰化蛋白在4-VO组和假手术组之间的乳酰化修饰水平存在显著差异。这些蛋白质的乳酰化位点在EA干预后趋于恢复。功能富集和聚类分析表明，这些蛋白质主要与包括核苷酸结合寡聚化结构域（NOD）样受体信号通路和突触小泡循环在内的途径相关。重要的是，我们评估了EA干预后Vdac3的乳酰化修饰水平是否增强。
EA改善了VD大鼠的认知功能障碍，其机制可能与海马组织中蛋白质乳酰化修饰的调节有关。它涉及多个靶点和途径，可能与Vdac3乳酰化修饰水平的提高有关。
