山苦瓜在老化引發肌少症小鼠模式中之效應

現代高齡化社會中，伴隨著年齡增長而日益加劇的活動功能退化為重要的公衛議題。肌少症為年齡相關肌肉質量減少、肌力與活動功能衰退的現象。伴隨老化的粒線體失能認為是影響肌少症的潛在因子。細胞衰老被認為是老化相關疾病發生的主要原因。細胞衰老為正常細胞永久停止分裂的狀態，具有獨特的生理特徵，如其衰老細胞分泌表型等。近期研究指出，山苦瓜可以上調粒線體氧化能力，並且改善睪丸剔除所誘導的肌肉流失及功能退化。在 ICR 小鼠模式中，山苦瓜亦被報導能改善肌力並降低疲勞。此實驗目的為以老齡誘發肌少症小鼠模式評估山苦瓜改善肌少症之潛力，並探討山苦瓜對於粒線體功能維持及細胞衰老的影響。三組 16.5 月齡 C57BL/6J 公鼠分別餵食 AIN-93G 飼料 (AN 組)、50% 蔗糖改良飼料不添加 (高蔗糖飼料, AH 組) 或添加 5% 山苦瓜全果凍乾粉 (AHB 組) 26週。另設計兩組 3.5 月齡 C57BL/6J 公鼠作為 AN 組及 AH 組之年輕控制組，分別以 YN 及 YH 表示。在餵食實驗飼料第 22 週時，山苦瓜回升老齡鼠中 Inverted screen test 表現至與年輕組相同水平 (p>0.05)。肌肉組織重量方面，山苦瓜補充顯著改善老齡鼠後肢小腿腓腸肌、比目魚肌、脛骨前肌、及趾伸長肌相對重量 (p<0.05)。肌肉切片及染色分析方面，山苦瓜補充增加腓腸肌及脛骨前肌中，大肌纖維橫截面積肌纖維比例 (p<0.05)。而腓腸肌中高琥珀酸脫氫酶活性肌纖維比例亦於 AHB 組高於 AH 組 (p<0.05)。苦瓜補充上調腓腸肌粒線體相關基因 Pgc1a、Ucp2，以及第一型肌纖維型態指標 Myh7 之mRNA 表現，並且下調第二型肌纖維型態指標 Myh4 mRNA 表現 (p<0.05)。此外，將 AN、AH、YN、及YH 組之數據以雙因子變異數分析後發現，腓腸肌、肝臟，及腎臟中衰老相關基因 mRNA 表現受到高齡上調 (p<0.05)。苦瓜補充下調肝臟及附睪周圍白色脂肪組織中 p16 基因表現 (p<0.05)，但並未影響肌肉中衰老相關基因 mRNA 表現 (p>0.05)。本研究證實了苦瓜補充可以改善老齡鼠肌肉功能及粒線體氧化能力，而這可能是透過促進粒線體生合成、改善對抗氧化壓力之能力、及促進骨骼肌中肌纖維轉變來達成。總結來說，山苦瓜補充能夠作為預防肌少症的有效策略。

關鍵字

山苦瓜 (Momordica Charantia) ；肌少症；粒線體；細胞衰老；老化

並列摘要

Sarcopenia, an age-related decline in muscle mass, strength, and physical function, is of great concern in the public health of ageing societies. Mitochondrial dysfunction, a hallmark of aging, is thought to play a major role in the pathogenesis of sarcopenia. Cellular senescence, a response characterized by a stable growth arrest and other phenotypes including a proinflammatory secretome, has been implicated as a major cause of age-related diseases. While wild bitter gourd has been reported to up-regulate mitochondrial oxidative capacity, improve exercise performance and reduce fatigue in castrated and ICR mice, this study aims to evaluate the effect of wild bitter gourd on mitochondrial oxidative capacity in an age-induced sarcopenia mouse model. Three groups of aging C57BL/6J male mice (16.5-month old) were fed the AIN-93G diet (the AN group) or its modified versions, which contained 50% w/w sucrose without (the AH group) or with 5% w/w wild bitter gourd powder (BGP) supplementation (the AHB group) for 26 weeks. Two more groups of 3-month old mice served as the young controls for AN AH group, denoted as YN group and YH group. At the 22nd week of the feeding period, the latency to fall and holding impulse in the inverted screen test of the AHB group were 19% and 10% higher than the AH group respectively, and were comparable to the young groups (p>0.05). At necropsy, BGP supplementation restored the age-related decline in the relative gastrocnemius (GAS), soleus, tibialis anterior, and extensor digitorum longus weight (p<0.05). The percentage of large cross section area (CSA) fibers in GAS and TA of the AHB group was higher than the AH group for 9.71 and 18.92% respectively (p<0.05).The percentage of high succinate dehydrogenase (SDH) activity fibers of the AHB group increased 23% in GAS comparing to the AH group (p<0.05). Compared to the AH group, the AHB mice showed up-regulated mRNA expressions of the Pgc1α gene, the master regulator of mitochondrial biogenesis, Ucp2 (ubiquitous uncoupling protein) and Myh7 (marker of type I fiber) genes and down-regulated Myh4 (type II fiber marker) in the GAS muscle (p<0.05). On the other hand, results from two-way ANOVA of data from AN, AH, YN and YH groups showed significant up-regulations of senescence-related genes in the GAS, liver and kidney of aged mice (p<0.05). The AHB group showed downregulated p16 mRNA gene expression in liver and EWAT. Nevertheless, expression levels of the senescence related genes were comparable to the AH group in the GAS of AHB group (p>0.05). In conclusion, these results suggested that BGP could improve muscle function and mitochondrial oxidative capacity, probably through increasing mitochondrial biogenesis and through inducing fiber type conversion in skeletal muscle and might provide a potential strategy to prevent sarcopenia.

並列關鍵字

Wild bitter gourd ； sarcopenia ； mitochondria ； cellular senescence ； aging

參考文獻

Acosta, J.C., O'Loghlen, A., Banito, A., Guijarro, M.V., Augert, A., Raguz, S., & Gil, J. (2008). Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence. Cell, 133(6), 1006-1018

Google Scholar

Alam, M.A., Uddin, R., Subhan, N., Rahman, M.M., Jain, P., & Reza, H.M. (2015). Beneficial role of bitter melon supplementation in obesity and related complications in metabolic syndrome. J Lipids, 2015, 496169

Google Scholar

Alcorta, D.A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., & Barrett, J.C. (1996). Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proceedings of the National Academy of Sciences, 93(24), 13742-13747

Google Scholar

Amara, C.E., Shankland, E.G., Jubrias, S.A., Marcinek, D.J., Kushmerick, M.J., & Conley, K.E. (2007). Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo. Proceedings of the National Academy of Sciences, 104(3), 1057-1062

Google Scholar

Arnold, D., Matthews, P., & Radda, G. (1984). Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magnetic resonance in medicine, 1(3), 307-315

Google Scholar

國際替代計量

山苦瓜在老化引發肌少症小鼠模式中之效應

未授權

主題瀏覽