Mao Jing, Li Ya, Feng Suxiang, Liu Xuefang, Tian Yange, Bian Qingqing, Li Junzi, Hu Yuanyuan, Zhang Lanxi, Ji Huige, Li Suyun
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.
Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China.
Front Pharmacol. 2020 Dec 17;11:587176. doi: 10.3389/fphar.2020.587176. eCollection 2020.
Skeletal muscle dysfunction, a striking systemic comorbidity of chronic obstructive pulmonary disease (COPD), is associated with declines in activities of daily living, reductions in health status and prognosis, and increases in mortality. Bufei Jianpi formula (BJF), a traditional Chinese herbal formulation, has been shown to improve skeletal muscle tension and tolerance via inhibition of cellular apoptosis in COPD rat models. This study aimed to investigate the mechanisms by which BJF regulates the adenosine monophosphate-activated protein kinase (AMPK) pathway to improve mitochondrial function and to suppress mitophagy in skeletal muscle cells. Our study showed that BJF repaired lung function and ameliorated pathological impairment in rat lung and skeletal muscle tissues. BJF also improved mitochondrial function and reduced mitophagy via the AMPK signaling pathway in rat skeletal muscle tissue. , BJF significantly improved cigarette smoke extract-induced mitochondrial functional impairment in L6 skeletal muscle cells through effects on mitochondrial membrane potential, mitochondrial permeability transition pores, adenosine triphosphate production, and mitochondrial respiration. In addition, BJF led to upregulated expression of mitochondrial biogenesis markers, including AMPK-α, PGC-1α, and TFAM and downregulation of mitophagy markers, including LC3B, ULK1, PINK1, and Parkin, with increased expression of downstream markers of the AMPK pathway, including mTOR, PPARγ, and SIRT1. In conclusion, BJF significantly improved skeletal muscle and mitochondrial function in COPD rats and L6 cells by promoting mitochondrial biogenesis and suppressing mitophagy via the AMPK pathway. This study suggests that BJF may have therapeutic potential for prophylaxis and treatment of skeletal muscle dysfunction in patients with COPD.
骨骼肌功能障碍是慢性阻塞性肺疾病（COPD）一种显著的全身性合并症，与日常生活活动能力下降、健康状况和预后降低以及死亡率增加有关。补肺健脾方（BJF）是一种传统中药配方，在COPD大鼠模型中已显示出通过抑制细胞凋亡来改善骨骼肌张力和耐受性。本研究旨在探讨BJF调节腺苷单磷酸激活蛋白激酶（AMPK）途径以改善线粒体功能并抑制骨骼肌细胞线粒体自噬的机制。我们的研究表明，BJF修复了大鼠肺和骨骼肌组织的肺功能并改善了病理损伤。BJF还通过大鼠骨骼肌组织中的AMPK信号通路改善了线粒体功能并减少了线粒体自噬。此外，BJF通过影响线粒体膜电位、线粒体通透性转换孔、三磷酸腺苷生成和线粒体呼吸，显著改善了香烟烟雾提取物诱导的L6骨骼肌细胞线粒体功能损伤。此外，BJF导致线粒体生物发生标志物（包括AMPK-α、PGC-1α和TFAM）的表达上调，线粒体自噬标志物（包括LC3B、ULK1、PINK1和Parkin）的表达下调，同时AMPK途径下游标志物（包括mTOR、PPARγ和SIRT1）的表达增加。总之，BJF通过AMPK途径促进线粒体生物发生并抑制线粒体自噬，显著改善了COPD大鼠和L6细胞的骨骼肌和线粒体功能。本研究表明，BJF可能对COPD患者骨骼肌功能障碍的预防和治疗具有治疗潜力。
