PDF(Pubmed)
Abstract：
Cancer-related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection (SFI) in managing CRF, focusing on its mechanistic action in skeletal muscle. We utilized a CRF mouse model to examine the effects of SFI on physical endurance, monitoring activity levels, swimming times and rest periods. Proteomic analysis of the gastrocnemius muscle was performed using isobaric tags and liquid chromatography-tandem mass spectrometry to map the muscle proteome changes post-SFI treatment. Mitochondrial function in skeletal muscle was assessed via ATP bioluminescence assay. Furthermore, the regulatory role of the hypoxia inducible factor 1 subunit alpha (HIF-1α) signalling pathway in mediating SFI\'s effects was explored through western blotting. In CRF-induced C2C12 myoblasts, we evaluated cell viability (CCK-8 assay), apoptosis (flow cytometry) and mitophagy (electron microscopy). The study also employed pulldown, luciferase and chromatin immunoprecipitation assays to elucidate the molecular mechanisms underlying SFI\'s action, particularly focusing on the transcriptional regulation of PINK1 through HIF-1α binding at the PINK1 promoter region. Our findings reveal that SFI enhances physical mobility, reduces fatigue symptoms and exerts protective effects on skeletal muscles by mitigating mitochondrial damage and augmenting antioxidative responses. SFI promotes cell viability and induces mitophagy while decreasing apoptosis, primarily through the modulation of HIF-1α, PINK1 and p62 proteins. These results underscore SFI\'s efficacy in enhancing mitochondrial autophagy, thereby offering a promising approach for ameliorating CRF. The study not only provides insight into SFI\'s potential therapeutic mechanisms but also establishes a foundation for further exploration of SFI interventions in CRF management.
摘要：
癌症相关性疲劳(CRF)显著影响癌症患者的生活质量。本研究调查了参芪扶正注射液（SFI）在治疗CRF中的治疗潜力，专注于其在骨骼肌中的机械作用。我们利用CRF小鼠模型来检查SFI对身体耐力的影响，监测活动水平，游泳时间和休息时间。使用等量异位标签和液相色谱-串联质谱法进行腓肠肌的蛋白质组学分析以绘制SFI处理后的肌肉蛋白质组变化。通过ATP生物发光测定法评估骨骼肌中的线粒体功能。此外，通过蛋白质印迹法探讨了缺氧诱导因子1亚基α（HIF-1α）信号通路在介导SFI效应中的调节作用。在CRF诱导的C2C12成肌细胞中，我们评估了细胞活力（CCK-8测定），细胞凋亡（流式细胞术）和线粒体自噬（电子显微镜）。这项研究还采用了下拉法，荧光素酶和染色质免疫沉淀试验，以阐明SFI作用的分子机制，特别关注PINK1通过HIF-1α结合在PINK1启动子区域的转录调节。我们的研究结果表明，SFI增强了身体活动能力，减轻疲劳症状，并通过减轻线粒体损伤和增强抗氧化反应对骨骼肌发挥保护作用。SFI促进细胞活力并诱导线粒体自噬，同时减少细胞凋亡，主要通过HIF-1α的调制，PINK1和p62蛋白。这些结果强调了SFI在增强线粒体自噬方面的功效，从而为改善CRF提供了一种有希望的方法。该研究不仅深入了解SFI的潜在治疗机制，而且为进一步探索SFI干预措施在CRF管理中的应用奠定了基础。
