| 研究生: |
范氏青香 Pham, Thi Thanh Huong |
|---|---|
| 論文名稱: |
使用微粒子影像流速儀研究潛在藥物對改善老化秀麗桿線蟲肌少症之效果 Study of potential pharmaceutical interventions on ameliorating sarcopenic phenotypes in aging Caenorhabditis elegans using a micro-particle image velocimetry system |
| 指導教授: |
莊漢聲
Chuang, Han-Sheng |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 生物醫學工程學系 Department of BioMedical Engineering |
| 論文出版年: | 2022 |
| 畢業學年度: | 110 |
| 語文別: | 英文 |
| 論文頁數: | 75 |
| 中文關鍵詞: | 秀麗隱桿線蟲 、衰老 、肌少症 、骨骼肌 、β-羥基丁酸 、熊果酸 、番茄鹼 、天然h萃取物 、藥物干預 、微粒子影像速度分析 、動能分析 、微流晶片 |
| 外文關鍵詞: | C. elegans, aging, sarcopenia, skeletal muscle, β-hydroxybutyric acid, Ursolic acid, Tomatidine, natural extracts, pharmaceutical intervention, micro-particle image velocimetry, kinetic power analysis, microfluidics chip |
| 相關次數: | 點閱:129 下載:2 |
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在尋求健康老齡化的過程中,面對肌少症是項持久的挑戰,肌少症是一種肌肉逐漸減少,會導致力量、敏捷性下降和疲勞增加的症候群。雖然原發性肌少症在健康個體的衰老過程中是自然發生的,但慢性發炎的疾病也可能造成次發性肌少症。儘管肌少症的治療主要為阻力訓練,但阻力訓練並不適合所有人,尤其是運動能力有限的患者或無行動能力的老年。因此,營養保健食品和藥物干預的措施逐漸成為一種改善肌肉流失的新方法。因此肌少症患者的另一種替代方法是使用營養或藥物作為預防或緩解措施。大量研究證明,幾種天然提取物可以有益於肌肉健康,然而對肌肉減少症的確切影響仍然未知,且目前研究方法效率較低以及需要冗長的臨床試驗。
為了解決這些問題,我們評估了 3 種選定化合物(β-羥基丁酸、熊果酸和番茄鹼),針對秀麗隱桿線蟲的壽命、後代數量、活性氧化物質、肌肉外觀(肌肉評分量表)和運動表現(動能分析)做量化觀察。整體健康結果表明,暴露於 β-羥基丁酸 (βHB) 和熊果酸可延長壽命,且均提高了蠕蟲的繁殖能力。在線蟲肌肉質量評估中,βHB 和補充劑改善了肌肉外觀。關於運動表現所做的動能分析,從微流晶片獲得的結果與在載玻片上測試沒有顯著差異,且在衰老期表現出高靈敏度。儘管動能結果與肌肉評分結果並不完全一致,但兩項評估都提供了藥物對肌肉健康有益的相關證據。
本論文了研究βHB、熊果酸和番茄鹼的對秀麗隱桿線蟲健康和肌少症的改善。另一方面,動能分析專用的微晶片的可行性得到了驗證。未來期望可以提高性能,從而達到優化和高通量篩選的目標。
In the search for healthy aging, muscle disorders, including loss of muscle mass, function, and impaired muscle metabolism, become a persistent challenge since it reduces muscular strength and performance in physical activities. Despite being the most effective treatment, resistance training is not suitable for all groups of people, especially patients with limited ability to exercise. Hence, nutraceutical and pharmaceutical interventions are rising as a novel approach to ameliorate senescence-caused muscle loss. Numerous studies have proven that several natural extracts could benefit muscle health, but the exact impact on sarcopenia is still unknown. In addition, the drug and supplement discovery process has slowed down due to inefficient methods and lengthy clinical trials.
To tackle this problem, we evaluated the anti-sarcopenic effects of three selected compounds (β-hydroxybutyric acid, Ursolic acid, and Tomatidine) on the nematode Caenorhabditis elegans in terms of lifespan, progeny number, reactive oxygen species level, muscle appearance, and motility. The results on the overall health of the worms showed that worms exposed to β-hydroxybutyric acid (βHB) and Ursolic acid led to lifespan extension by 22.2% and 18.2%, respectively. All treatments enhanced the reproductivity of the worms. In the nematode muscle quality assessment, βHB and the supplements improved muscle appearance, as indicated by the muscle confocal scanning, phenotypic scoring, and the gap ratio calculation. Regarding kinetic power analysis, results obtained from the microchip had no significant differences from the standard glass-slides counterpart, ensuring that the chip platform is suitable for the motility assay. Unlike the muscle phenotype scoring, in which improvement was the most obvious in the middle-aged phase, the kinetic power analysis demonstrated high sensitivity in the senescence period. Although kinetic power outcomes did not fully correspond with the muscle scoring results, both assessments supported that muscle health benefits yielded from the pharmaceutical substances.
This thesis highlights the health benefits and anti-sarcopenic effects of βHB, Ursolic acid, and Tomatidine. On the other hand, the feasibility of a kinetic power-specialized microchip was also validated by the standard setup. In the future, this minimal design can be upgraded with automated worm loading and scaled up with multiple wells for various conditions to improve the platform performance, thus reaching the optimization and high-throughput goal.
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