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Muscle Structure and Function Recovery: Adalimumab‐Calcium Channel Synergy in Post–Ischemic Stroke Sarcopenia

作者:Qi Hu, Xiongwei Zhang, Zeyang Zhang, Shu-fei Ou, Yuan‐Lin Gao, Dan Tian, Yanning Jiang, Xin‐Ran Min, Ao‐Tao Zhao, Jia‐Min Zou, J Zeng, Qian Pu, Ruocong Yang, Nan Zeng · 发表于:Journal of Cachexia Sarcopenia and Muscle · 年份:2025 · DOI:10.1002/jcsm.70097 · 被引用次数:1 · 研究领域:Muscle Physiology and Disorders、Nutrition and Health in Aging、GDF15 and Related Biomarkers

ABSTRACT Background Adalimumab, a TNF‐α inhibitor, is widely used clinically. Recent studies suggest Adalimumab can improve muscle damage after ischemic stroke (IS), but its protective mechanisms remain unclear. This study investigates the effect of adalimumab on muscle structure post‐IS and the role of calcium balance in muscle strength, while validating their synergistic effect. Methods This study investigates the effects of adalimumab and GV‐58 on muscle structure and function in male middle cerebral artery occlusion (MCAO) rat models using behavioural, imaging, pathological and WB experiments. In vitro mechanisms are explored with L6 and primary muscle cells. Results The results of the present study showed a significant decrease in motor function in IS‐induced sarcopenia (ISS) rats, as evidenced by shortened length (−47.56%, p < 0.001), reduced weight (−43.79%, p < 0.001) and reduced cross‐sectional area of myofibroblasts (−38.58%, p < 0.001) in the soleus muscle as compared to the sham group. Inflammatory factors such as IL‐1β, IL‐6, TNF‐α and reactive oxygen species (ROS) levels were significantly elevated in the muscles of ISS rats (3.10‐fold, 3.78‐fold, 2.29‐fold, 2.80‐fold, p < 0.001). Molecular mechanism studies showed that TNF‐α, MAFbx and MuRF1 protein expression was down‐regulated, and IL‐10 and MyoD1 expression was up‐regulated in muscle tissues of ISS rats. RNA‐seq implicated the Ca 2+ signalling pathway in ISS‐related muscle weakness. Muscle streng...