Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Province Clinical Research Center for Medical Imaging, Wuhan, 430022, China.
J Neuroinflammation. 2023 Apr 17;20(1):94. doi: 10.1186/s12974-023-02773-2.
The cholinergic anti-inflammatory pathway (CAP) has been widely studied to modulate the immune response. Current stimulating strategies are invasive or imprecise. Noninvasive low-intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for targeted neuronal modulation. However, its mechanisms and physiological role on myocarditis remain poorly defined.
The mouse model of experimental autoimmune myocarditis was established. Low-intensity pulsed ultrasound was targeted at the spleen to stimulate the spleen nerve. Under different ultrasound parameters, histological tests and molecular biology were performed to observe inflammatory lesions and changes in immune cell subsets in the spleen and heart. In addition, we evaluated the dependence of the spleen nerve and cholinergic anti-inflammatory pathway of low-intensity pulsed ultrasound in treating autoimmune myocarditis in mice through different control groups.
The echocardiography and flow cytometry of splenic or heart infiltrating immune cells revealed that splenic ultrasound could alleviate the immune response, regulate the proportion and function of CD4+ Treg and macrophages by activating cholinergic anti-inflammatory pathway, and finally reduce heart inflammatory injury and improve cardiac remodeling, which is as effective as an acetylcholine receptor agonists GTS-21. Transcriptome sequencing showed significant differential expressed genes due to ultrasound modulation.
It is worth noting that the ultrasound therapeutic efficacy depends greatly on acoustic pressure and exposure duration, and the effective targeting organ was the spleen but not the heart. This study provides novel insight into the therapeutic potentials of LIPUS, which are essential for its future application.
胆碱能抗炎通路 (CAP) 已被广泛研究用于调节免疫反应。目前的刺激策略具有侵入性或不精确性。非侵入性低强度脉冲超声 (LIPUS) 已越来越多地用于靶向神经元调节。然而，其在心肌炎中的机制和生理作用仍未得到明确界定。
建立实验性自身免疫性心肌炎小鼠模型。低强度脉冲超声靶向脾脏以刺激脾脏神经。在不同的超声参数下，进行组织学测试和分子生物学检测，以观察脾脏和心脏中炎症病变和免疫细胞亚群的变化。此外，我们通过不同的对照组评估了低强度脉冲超声治疗小鼠自身免疫性心肌炎中脾脏神经和胆碱能抗炎通路的依赖性。
超声刺激脾脏可通过激活胆碱能抗炎通路减轻免疫反应，调节 CD4+Treg 和巨噬细胞的比例和功能，从而减轻心脏炎症损伤和改善心脏重构，这与乙酰胆碱受体激动剂 GTS-21 一样有效。超声调制导致转录组测序显示出明显差异表达的基因。
值得注意的是，超声治疗效果在很大程度上取决于声压和暴露时间，有效靶向器官是脾脏而不是心脏。本研究为 LIPUS 的治疗潜力提供了新的见解，这对其未来的应用至关重要。
