| 摘要: | Cisplatin (CP)是一種廣泛用於治療許多癌症的化療藥物，雖然可以抑制腫瘤的生長，但對於組織器官也會造成一定的副作用，其中肌肉的流失與萎縮為臨床上主要常見的情形。目前對於cisplatin造成肌肉萎縮之機制尚不明確，但與其肌肉蛋白質狀態不平衡及凋亡路徑有關。辣椒素 (capsaicin, CAP) 為辣椒中最主要的成分且具有熱及辛辣的口感，具有控制疼痛、抑制發炎、抗氧化以及抗腫瘤的效果，另外研究指出對於肌肉萎縮有治療的潛力並能促進肌肉的質量，然而辣椒素對於cisplatin所造成肌肉傷害及萎縮其保護的機制尚未有文獻探討，因此本實驗目的為探討介入辣椒素對於化療藥物cisplatin在體內體外誘導肌肉萎縮的模式是否有改善的效果。結果顯示給予cisplatin於骨骼肌細胞株C2C12會促使蛋白質異化作用造成骨骼肌細胞的存活率降低且細胞型態有萎縮之現象，肌肉微管長度有明顯減少的情況，而介入不同濃度的辣椒素，隨其劑量的增加具有回復化療藥物cisplatin所導致的肌肉萎縮情形，具有增加蛋白質生合成路徑Akt, mTOR的表現量並降低肌肉分解蛋白Myostatin, MAFbx, MuRF-1表現以及降低凋亡相關蛋白表現進而減輕肌肉的流失和萎縮。此外，辣椒素在體內實驗中可以回復肌纖維面積、減輕體重流失及增加肌拉力表現以改善cisplatin造成肌肉流失及萎縮。上述結果顯示化療藥物cisplatin會導致蛋白質調控失衡，使其分解大於合成以促使肌肉萎縮，然而，預先介入辣椒素再給予化療藥物cisplatin可減輕骨骼肌肉的萎縮及損傷。因此，辣椒素具有減緩化療藥物對於骨骼肌肉萎縮的預防效果，具有開發成改善化療副作用保健食品之潛力。
Cisplatin (CP) is a widely used chemotherapeutic drug which causes a lot of adverse effects on different organs and tissues, among these side effects, skeletal muscle loss and atrophy are the most common clinical symptoms. The molecular mechanism of cisplatin-induced muscle atrophy is not well understood. However, significant advances indicate that the cause of cisplatin is related to imbalance protein status and apoptosis. Capsaicin (CAP), is one of the major ingredients in chili peppers. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. It is reported to have therapeutic potential in muscle atrophy. However, the mechanisms underlying its protective effects on cisplatin-induced muscle loss and atrophy remain largely unknown. The purpose of this study was to investigate the effect of capsaicin on cisplatin-induced muscle loss and atrophy in vivo and in vitro. Our study results indicated that within cisplatin administration, C2C12 myotube displayed lower cell viability and showed a subset of hallmark signs typically recognized during atrophy, including severe reduction in myotube diameter, repression of Akt, mTOR protein expression. However, we demonstrated that administration of capsaicin could ameliorate cisplatin-induced muscle atrophy by up-regulation of Akt, mTOR, which stimulated protein synthesis in skeletal muscle and down-regulation of Myostatin, MAFbx, MuRF-1, the marker of protein degradation. Also, it could down-regulate apoptosis associated protein expression which caused by cisplatin. Furthermore, capsaicin significantly enhanced grip strength and alleviated cisplatin-induced body weight loss and gastrocnemius atrophy in vivo. In conclusion, these findings suggest that cisplatin lead to an imbalance between protein synthesis and protein degradation pathways, then capsaicin has protective effects against cisplatin-induced muscle atrophy. |
