表儿茶素缓解老年小鼠肌肉减少症的作用及其机制研究

刘美凤1, 2, 3, 5, 黄子唯1, 2, 4, 5, 刘爱玲1, 2, 4, 5, 屈志豪1, 2, 3, 5, 黄建安1, 2, 3, 5, 刘仲华1, 2, 3, 5, 张盛1, 2, 3, 5

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表儿茶素缓解老年小鼠肌肉减少症的作用及其机制研究

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Study on the Effect and Mechanism of Epicatechin in Alleviating Sarcopenia in Aged Mice

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摘要

衰老过程必然伴随着肌肉力量和质量下降,严重损害老年群体的健康和生活质量。表儿茶素(Epicatechin,EC)是茶叶中的主要次级代谢产物之一,具有多种生物学活性。已有研究揭示了EC对衰老过程的延缓作用,但其与衰老相关肌肉减少症的关系尚不明确。为探究EC对衰老相关肌肉减少症的影响及潜在机制,以自然衰老C57BL/6J小鼠为模型,通过动物行为学测试、肌肉指数测定、组织形态学分析、Elisa检测、转录组测序结合实时荧光定量PCR(RT-qPCR)技术等方法进行系统评估。结果表明,与对照组相比,EC处理显著提升了老年小鼠的抓力和耐力表现(P<0.05),并显著增加了腓肠肌、胫骨前肌和股四头肌的肌肉指数(P<0.05);EC处理组腓肠肌肌纤维面积更大,排列结构更规整;EC显著降低了老年小鼠体内炎症因子IL-6和TNF-α的水平(P<0.05)。通过转录组测序和RT-qPCR验证进一步发现,EC可能通过下调支链氨基酸(Branched-chain amino acid,BCAA)转氨酶基因BCAT1的表达,上调BCAA转氨酶基因BCAT2、BCAA转运体基因LAT1LAT2的表达,影响BCAA代谢相关基因的表达,进而调节肌肉蛋白质合成;同时上调骨骼肌分化相关基因MyoDMyoGMRF4MCKMyf5的表达,延缓老年小鼠的肌肉减少症。

Abstract

The aging process is inevitably accompanied by a decline in muscle strength and mass, severely impairing the health and quality of life of the elderly population. Epicatechin (EC) is one of the main secondary metabolites found in tea, possesses a variety of biological activities. Previous studies have revealed the anti-aging effects of EC, but its relationship with age-related sarcopenia remains unclear. To investigate the effects and underlying mechanisms of EC on age-related sarcopenia, this study employed naturally aged C57BL/6J mice as a model. A comprehensive evaluation was conducted using a series of methodologies, including animal behavioral tests, muscle index measurements, histological analysis, Elisa assays, transcriptome sequencing and RT-qPCR validation. The results show that compared with the control group, EC treatment significantly improved the grip strength and endurance performance of aged mice (P<0.05), and significantly increased the muscle index of the gastrocnemius, tibialis anterior, and quadriceps femoris muscles (P<0.05). The gastrocnemius muscle fibers in the EC treated group were larger in area and more regularly arranged. EC significantly reduced the levels of the inflammatory factors IL6 and TNFα in aged mice (P<0.05). Further transcriptomic sequencing and RT-qPCR validation reveal that EC might downregulate the expression of the BCAA transaminase gene BCAT1 and upregulate the expression of the BCAA transaminase gene BCAT2, as well as the BCAA transporter genes LAT1 and LAT2, thereby regulating muscle protein synthesis. Meanwhile, it could upregulate the expressions of skeletal muscle differentiation-related genes including MyoD, MyoG, MRF4, MCK and Myf5 to alleviate sarcopenia in aged mice.

关键词

表儿茶素 / 肌肉减少症 / 抗衰老

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刘美凤1, 2, 3, 5, 黄子唯1, 2, 4, 5, 刘爱玲1, 2, 4, 5, 屈志豪1, 2, 3, 5, 黄建安1, 2, 3, 5, 刘仲华1, 2, 3, 5, 张盛1, 2, 3, 5. 表儿茶素缓解老年小鼠肌肉减少症的作用及其机制研究[J]. 茶叶科学. 0
LIU Meifeng1, 2, 3, 5, HUANG Ziwei1, 2, 4, 5, LIU Ailing1, 2, 4, 5, QU Zhihao1, 2, 3, 5, HUANG Jian'an1, 2, 3, 5, LIU Zhonghua1, 2, 3, 5, ZHANG Sheng1, 2, 3, 5. Study on the Effect and Mechanism of Epicatechin in Alleviating Sarcopenia in Aged Mice[J]. Journal of Tea Science. 0
中图分类号: S571.1    Q946.84+1    R685   

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国家重点研发计划(2021YFD1601100)

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