中国组织工程研究

中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (32): 5172-5176.doi: 10.12307/2024.512

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

短链脂肪酸干预老年大鼠肌少症的作用及机制

徐  锐1，李燕燕2，徐  红1   

  1. 新疆维吾尔自治区人民医院，1老年医学中心，2心脏外科，新疆维吾尔自治区乌鲁木齐市  830054
  • 收稿日期:2023-09-14 接受日期:2023-10-21 出版日期:2024-11-18 发布日期:2023-12-29
  • 通讯作者: 徐红，博士，主任医师，新疆维吾尔自治区人民医院老年医学中心，新疆维吾尔自治区乌鲁木齐市 830054
  • 作者简介:徐锐，男，1986年生，新疆维吾尔自治区乌鲁木齐市人，汉族，在读博士，主治医师，主要从事老年肌少症、衰弱的基础研究。
  • 基金资助:
    新疆自然科学基金2021年(2021D01C163)，项目负责人：徐锐

Effect and mechanism of short-chain fatty acids in aged rats with sarcopenia

Xu Rui1, Li Yanyan2, Xu Hong1   

  1. 1Gerontology Center, 2Department of Cardiac Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • Received:2023-09-14 Accepted:2023-10-21 Online:2024-11-18 Published:2023-12-29
  • Contact: Xu Hong, MD, Chief physician, Gerontology Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • About author:Xu Rui, MD candidate, Attending physician, Gerontology Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • Supported by:
    the Natural Science Foundation of Xinjiang Uygur Autonomous Region, No. 2021D01C163 (to XR)

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摘要：


文题释义：

短链脂肪酸：是一类碳链较短的脂肪酸，主要由丁酸、乙酸和丙酸组成，是一种重要的肠道菌群代谢物，主要通过膳食纤维的发酵产生。它们在人体内具有重要的能量供给和多种生理功能，包括维持肠道健康、调节免疫功能、降低血脂和调节血糖等作用。最近大量研究显示短链脂肪酸对肌肉的能量代谢、运动功能起到积极的作用。
AMPK：即AMP依赖的蛋白激酶，是生物能量代谢调节的关键分子，为高血压、高脂血症、糖尿病等代谢性疾病的关键通路。它表达于各种代谢相关的器官中，能被机体各种刺激激活，包括细胞压力、运动和很多激素及能影响细胞代谢的物质。近期有研究显示短链脂肪酸可通过影响AMPK通路改善肌肉组织的炎症反应和糖脂代谢，可作为肌少症的一个关键通路分子。


背景：研究显示短链脂肪酸是一种潜在的骨骼肌能量代谢调节物，但具体机制尚不明确。

目的：探索短链脂肪酸对老年肌少症的作用及可能的相关机制。
方法：将SD大鼠随机分为对照组、肌少症组、肌少症+短链脂肪酸组，后2组大鼠采用摘除大鼠卵巢、1周后按体质量5 mg/kg皮下注射地塞米松、连续7 d给药的方案建立老年肌少症大鼠模型；对照组大鼠打开腹腔找到卵巢但不摘除，随即缝合腹腔。肌少症+短链脂肪酸组大鼠造模术后给予含有150 mmol/L短链脂肪酸的饮用水(乙酸钠600 mg/kg、丙酸钠200 mg/kg、丁酸钠200 mg/kg)，对照组及肌少症组大鼠给予等量的生理盐水，1次/d，连续4周。造模结束后测量大鼠双侧腓肠肌质量和体质量计算腓肠肌指数，评估造模是否成功。于造模成功后0，1，2，4周测量大鼠的摄食量、体质量及抓力；苏木精-伊红染色观察腓肠肌形态学改变；Western blot法检测腓肠肌中p-AMPK、p-ULK1蛋白的表达。

结果与结论：与对照组比较，肌少症组大鼠摄食量、体质量及抓力均显著降低(P < 0.05)，腓肠肌的湿质量显著降低(P < 0.05)，腓肠肌中p-AMPK和p-ULK1蛋白表达均显著降低(P < 0.05)；与肌少症组相比，肌少症+短链脂肪酸组大鼠摄食量、体质量、抓力、腓肠肌的湿质量及腓肠肌中p-AMPK和p-ULK1的蛋白表达显著增加(P < 0.05)。结果提示，短链脂肪酸可改善老年肌少症的症状，可能与骨骼肌中AMPK和ULK1蛋白水平增高有关。

https://orcid.org/0000-0002-6264-4536(徐锐)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 肌少症, AMPK, ULK1, 短链脂肪酸, 骨骼肌, 糖脂代谢

Abstract: BACKGROUND: Studies have shown that short-chain fatty acids (SCFAs) are a potential regulator of skeletal muscle energy metabolism, but the exact mechanism is unclear. 
OBJECTIVE: To observe the effect of SCFAs on aged rats with sarcopenia and to explore the underlying mechanism. 
METHODS: Sprague-Dawley rats were randomly divided into control group, sarcopenia group, and sarcopenia+SCFAs group (SCFAs group). In the latter two groups, rat models of sarcopenia were established using ovariectomized rats injected with 5 mg/kg dexamethasone for 7 days. In the control group, the abdominal cavity was only exposed but not removed, and then sutured. Rats in the SCFAs group were administered drinking water containing 150 mmol/L short-chain fatty acids, 600 mg/kg sodium acetate, 200 mg/kg sodium propionate, and 200 mg/kg sodium butyrate for 4 weeks. Rats in the control and sarcopenia groups were given the same volume of normal saline. Successful modeling was assessed by measuring the bilateral gastrocnemius muscle mass and body mass to calculate the gastrocnemius index after modeling. Food intake, body mass and grip strength of rats were measured at 0, 1, 2 and 4 weeks after successful modeling; morphological changes of gastrocnemius muscle were observed by hematoxylin-eosin staining; and the expression of p-AMPK and p-ULK1 proteins in gastrocnemius muscle was detected by western blot. 
RESULTS AND CONCLUSION: Compared with the control group, the sarcopenia group showed significantly decreased body mass, food intake, forelimb grip strength (P < 0.05), wet mass of gastrocnemius muscle (P < 0.05), and protein levels of p-AMPK and p-ULK1 (P < 0.05). Compared with the sarcopenia group, the SCFAs group showed a significant increase in food intake, body mass, grip strength, wet mass of gastrocnemius muscle, and protein levels of p-AMPK and p-ULK1 in gastrocnemius muscle (P < 0.05). All these findings indicate that SCFAs improve symptoms of sarcopenia in the elderly and may be associated with the upregulation of AMPK and ULK1 proteins in skeletal muscle.

Key words: sarcopenia, AMPK, ULK1, short-chain fatty acids, skeletal muscle, glucolipid metabolism

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