Hu Yuchi, Dai Songyuan, Chen Liling, Ma Xuejuan, Li Hao, Lu Yanan, Li Chuanxin, Chen Xinyun, Li Hongning, Lu Yanzhou, Huang Yimei, Zhao Lulu, Hua Baotong, Zhao Ling
Department of Cardiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
Department of Laboratory Zoology, Kunming Medical University, Kunming, Yunan, P.R. China.
Sci Rep. 2025 Jun 4;15(1):19613. doi: 10.1038/s41598-025-04397-3.
The potential benefits and underlying mechanisms of Vagus Nerve Stimulation (VNS) in the treatment of Chronic Congestive Heart Failure (CHF) remain insufficiently elucidated. Therefore, this study aims to investigate the therapeutic potential and mechanisms of VNS in treating CHF. In this study, models of CHF and VNS were established prior to performing echocardiography, H&E staining, and flow cytometry to evaluate the effects of VNS on pathological damage associated with CHF and myocardial mitochondrial dysfunction. Multi-omics analysis was conducted to identify changes in metabolites, gut microbiota, and gene expression following VNS treatment. Finally, QPCR was applied to measure levels of essential genes at the mRNA levels. VNS effectively enhances cardiac function, improves metabolic processes, and reduces inflammatory factor levels in dogs with CHF. VNS alleviates myocardial pathological damage, prevents the accumulation of ROS, and increases mitochondrial membrane potential. Multi-omics analysis identified five key metabolites, four key microorganisms, and sixty key genes. Furthermore, combined multi-omics analysis revealed key therapeutic targets, including three metabolites, four microorganisms, and sixteen genes. VNS significantly downregulates the mRNA expression levels of FSTL3, TNFRSF12A, and HBEGF. In summary, VNS has demonstrated effectiveness in the treatment of CHF. Key therapeutic targets identified include Kamahine C, FSTL3, TNFRSF12A, and HBEGF.
迷走神经刺激（VNS）治疗慢性充血性心力衰竭（CHF）的潜在益处和潜在机制仍未得到充分阐明。因此，本研究旨在探讨VNS治疗CHF的治疗潜力和机制。在本研究中，在进行超声心动图、苏木精-伊红（H&E）染色和流式细胞术之前，建立了CHF和VNS模型，以评估VNS对与CHF相关的病理损伤和心肌线粒体功能障碍的影响。进行多组学分析以确定VNS治疗后代谢物、肠道微生物群和基因表达的变化。最后，应用定量聚合酶链反应（QPCR）来测量关键基因在mRNA水平的表达。VNS能有效增强CHF犬的心功能，改善代谢过程，并降低炎症因子水平。VNS减轻心肌病理损伤，防止活性氧（ROS）积累，并增加线粒体膜电位。多组学分析确定了五种关键代谢物、四种关键微生物和六十个关键基因。此外，联合多组学分析揭示了关键治疗靶点，包括三种代谢物、四种微生物和十六个基因。VNS显著下调FSTL3、TNFRSF12A和HBEGF的mRNA表达水平。总之，VNS已证明对CHF治疗有效。确定的关键治疗靶点包括卡马辛C、FSTL3、TNFRSF12A和HBEGF。
