Tang Xue-Qin, Liao Ruo-Yi, Zheng Li-Jun, Yang Ling-Ling, Ma Zhi-Lin, Yi Chan, Liu Jin, Liu Jin-Can, Kuang Yi-Jin, Cai Hua-An, Huang Liang
Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.
The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China.
Ann Transl Med. 2022 Dec;10(24):1350. doi: 10.21037/atm-22-5443.
Post-stroke depression (PSD) is one of the most common and serious sequelae of stroke. The pathogenesis of PSD involves both psychosocial and biological mechanisms, and aerobic exercise is a potential therapeutic target. We conducted an in-depth exploration of the protective mechanisms of aerobic exercise in a PSD mouse model.
In this study, C57BL/6 mice were used as the research objects, and a PSD mouse model was established by combining middle cerebral artery occlusion and chronic unpredictable mild stimulation. Real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, adeno-associated virus microinjection technology, co-immunoprecipitation, fluorescence in-situ hybridization, and western blotting were performed. A moderate-load treadmill exercise was used for aerobic exercise intervention. The moderate-intensity aerobic exercise training method adopted 0 slopes and treadmill adaptation training for 5 days. We verified the effects of aerobic exercise on the nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain--like receptor protein 3 (NLRP3) inflammasome/5-hydroxytryptamine (5-HT) pathway.
Aerobic exercise effectively alleviated the neurological damage caused by PSD (P<0.01). The results from the PSD mouse model were consistent with those of the cell experiments. Moreover, overexpression of irisin improves depression-like behavior in PSD mice. We confirmed that aerobic exercise is involved in PSD through 5-HT, which inhibits NF-κB/NLRP3 inflammasome initiation through irisin and alleviates mitochondrial damage under stress by reducing calcium overload, thereby inhibiting NLRP3 inflammasome activation.
Aerobic exercise reversed the NF-κB/NLRP3 inflammasome/5-HT pathway by upregulating irisin expression to alleviate PSD.
中风后抑郁症（PSD）是中风最常见且最严重的后遗症之一。PSD的发病机制涉及心理社会和生物学机制，有氧运动是一个潜在的治疗靶点。我们对有氧运动在PSD小鼠模型中的保护机制进行了深入探索。
在本研究中，以C57BL/6小鼠作为研究对象，通过大脑中动脉闭塞联合慢性不可预测轻度刺激建立PSD小鼠模型。进行实时定量聚合酶链反应、酶联免疫吸附测定、腺相关病毒显微注射技术、免疫共沉淀、荧光原位杂交和蛋白质免疫印迹法。采用中等负荷跑步机运动进行有氧运动干预。中等强度有氧运动训练方法采用0坡度，进行5天的跑步机适应性训练。我们验证了有氧运动对核因子κB（NF-κB）/核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体/5-羟色胺（5-HT）通路的影响。
有氧运动有效减轻了PSD所致的神经损伤（P<0.01）。PSD小鼠模型的结果与细胞实验结果一致。此外，鸢尾素过表达改善了PSD小鼠的抑郁样行为。我们证实有氧运动通过5-HT参与PSD，5-HT通过鸢尾素抑制NF-κB/NLRP3炎性小体的启动，并通过减少钙超载减轻应激状态下的线粒体损伤，从而抑制NLRP3炎性小体的激活。
有氧运动通过上调鸢尾素表达逆转NF-κB/NLRP3炎性小体/5-HT通路，从而减轻PSD。
