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標題: | 山苦瓜萃取物協助 IGF-1 透過 PI3K/Akt 路徑促進小鼠骨骼肌前驅細胞生長 Wild Bitter Melon Extract Assists IGF-1 in Promoting Mouse Skeletal Muscle Cell Proliferation Through PI3K/Akt Pathway |
作者: | Yii-Tzu Huang 黄苡慈 |
指導教授: | 黃青真 |
關鍵字: | 山苦瓜,肌肉細胞,類胰島素生長因子-1,粒線體, Wild bitter gourd,C2C12 myoblasts,IGF-1,Mitochondria, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | 肌少症 (Sarcopenia) 是指隨著年紀上升,肌肉質量、力量及功能逐漸下降,大致是由於神經退化、長期活動量降低、體內內分泌賀爾蒙雄激素睪固酮 (testosterone)、類胰島素生長因子-1 (Insulin-like growth factor-1, IGF-1) 分泌減少所導致骨骼肌修復能力降低或肌纖維蛋白質分解加速。目前改善肌少症的方針主要為運動及營養補充,亦有許多研究朝向調控肌肉生長並壯大肌肉的路徑著手。山苦瓜可調節諸多生理活性,包括血糖、血脂、免疫及改善代謝異常,然而其對於肌肉生長的研究至今甚少。因此,本研究目標為以細胞模式及動物模式探討山苦瓜對於骨骼肌生長與功能的影響。
在細胞模式中,本實驗以山苦瓜萃物處理 C2C12 肌肉前驅細胞 (myoblast) 48 小時,探討山苦瓜是否可以促進細胞增生。結果顯示,1758 品系山苦瓜乙酸乙酯萃物 (1758 EAE) 單獨處理 myoblast 雖無法使細胞數目增加,但可以促進粒線體功能指標 citrate synthase 活性。再者,1758 EAE 與 IGF-1 共同處理之下,可以顯著增加 myoblast 細胞數目。以 PI3K 抑制劑 LY294002 抑制 IGF-1 傳遞路徑後,1758 EAE 協助 IGF-1 促進細胞增生之效應消失。進一步以西方墨點法分析蛋白質表現量,結果顯示,共處理 myoblast 一小時,1758 EAE 可以幫助 IGF-1增加下游傳遞路徑 Akt 磷酸化表現量。在動物模式中,本研究將不同品系 4 % 山苦瓜全果凍乾粉添加於高脂飲食中,並餵食 C57BL/6J 公鼠進行短期 4 週動物試驗。結果顯示,山苦瓜可以減低高脂飲食誘導之體重、白色脂肪堆積及胰島素阻抗情形,並能增加腓腸肌相對重量,而 1758 品系能進一步促進小鼠腓腸肌 IGF-1、Igf1r、Akt2、Hk2 基因表現。綜合以上,1758 山苦瓜可以協同 IGF-1 促進肌肉前驅細胞增生,並具有調控骨骼肌 IGF-1 下游傳遞路徑的潛力。 Sarcopenia is a gradual loss of skeletal muscle mass, function and strength associated with ageing. The main causes of sarcopenia include loss of motor neurons, physical inactivity or a decline in anabolic hormones such as testosterone and insulin-like growth factor-1 (IGF-1), which lead to reduction in regenerative capacity or increased protein degradation in skeletal muscle. Currently, the validated strategies are exercise and nutritional supplementation. On the other hand, the pathways which stimulate muscle hypertrophy have been actively investigated. Wild bitter gourd (WBG) has been shown to ameliorate metabolic disorders such as hyperglycemia and hyperlipidemia. However, little research was focussed on muscle growth. Hence, the aim of this study is to examine the effect of WBG on skeletal muscle growth and function as an initial approach. In the cell model, C2C12 myoblasts were treared with WBG extracts for 48 hours to determine the proliferation ability of WBG. The results showed that the WBG cultivar 1758 ethyl acetate extract (EAE) enchanced the activity of citrate synthase, a marker of mitochondria, and, in the presence of IGF-I, promoted myoblasts proliferation. The effect of 1758 EAE on IGF-1-mediated proliferation was diminished in the presence of PI3K inhibitor LY294002. Western blot analysis further showed that 1758 EAE increased Akt phosphorylation of C2C12 myoblasts in the presence of IGF-I after 1 hour of treatment. In the short-term animal study, C57/BL/6J male mice were fed a high-fat diet supplemented without or with 4% various cultivars of WBG for 4 weeks. WBG reduced total body weight, white adipose mass, insulin resistance, and increased relative gastrocnemius muscle mass. 1758 WBG specifically enhanced mRNA expression levels of IGF-1, Igf1r, Akt2, Hk2 in gastrocnemius muscle. These results indicate that 1758 WBG may enhance the proliferation effect of IGF-1 in myoblasts, and might regulate IGF-1 signaling pathway in skeletal muscle. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7592 |
DOI: | 10.6342/NTU201704166 |
全文授權: | 同意授權(全球公開) |
電子全文公開日期: | 2023-08-23 |
顯示於系所單位: | 生化科技學系 |
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