時(shí)間：2025-07-25
最新研究揭示關(guān)鍵機(jī)制
泰國科研團(tuán)隊(duì)在《生理學(xué)報(bào)告》發(fā)表突破性研究，首次揭示維生素D不同形式在對(duì)抗血管緊張素II誘導(dǎo)的肌肉萎縮中的雙刃劍效應(yīng)。這項(xiàng)由清邁大學(xué)領(lǐng)銜的細(xì)胞實(shí)驗(yàn)研究，為慢性病患者肌肉萎縮的精準(zhǔn)干預(yù)提供了全新視角。
研究聚焦腎素-血管緊張素系統(tǒng)過度激活引發(fā)的肌肉消耗問題，利用C2C12小鼠肌管細(xì)胞模型，模擬慢性病患者常見的病理狀態(tài)。通過對(duì)比普通維生素D3（膽鈣化醇）與其活性形式骨化三醇（1,25VD3）的作用差異，發(fā)現(xiàn)關(guān)鍵機(jī)制：
1.形態(tài)學(xué)保護(hù)差異：100nM維生素D3與降壓藥氯沙坦同樣具有維持肌管直徑的作用，而1-10nM骨化三醇反而激活MuRF1、atrogin-1等肌肉分解關(guān)鍵酶，提示活性維生素D可能加劇蛋白質(zhì)分解。
2.自噬通路擾動(dòng)：骨化三醇處理顯著上調(diào)自噬標(biāo)記物L(fēng)C3B-II（增幅達(dá)2.3倍），同時(shí)降低p62/SQSTM1蛋白水平，揭示其通過異常激活自噬途徑促進(jìn)肌肉消耗。
3.氧化應(yīng)激失衡：骨化三醇組出現(xiàn)活性氧簇（ROS）爆發(fā)性增長（較對(duì)照組升高58%），NADPH氧化酶-2過量產(chǎn)生，而超氧化物歧化酶和過氧化氫酶等抗氧化防御機(jī)制響應(yīng)不足，形成惡性循環(huán)。
"這顛覆了我們對(duì)維生素D代謝物的傳統(tǒng)認(rèn)知。" 通訊作者M(jìn)uthita Hirunsai博士指出，"研究證明維生素D3本身具有直接肌肉保護(hù)作用，而臨床常用的活性形式骨化三醇在特定病理環(huán)境下可能產(chǎn)生負(fù)面效應(yīng)。"
該研究首次系統(tǒng)闡明兩種維生素D形式在肌肉萎縮中的相反作用，為慢性腎病、心衰等伴隨血管緊張素系統(tǒng)激活的疾病治療提供重要參考。專家建議，臨床補(bǔ)充維生素D時(shí)應(yīng)充分考慮患者病理狀態(tài)，監(jiān)測(cè)氧化應(yīng)激指標(biāo)，避免活性形式維生素D的潛在風(fēng)險(xiǎn)。
目前研究團(tuán)隊(duì)正著手開展動(dòng)物實(shí)驗(yàn)，進(jìn)一步驗(yàn)證不同維生素D形式的體內(nèi)效應(yīng)。此項(xiàng)發(fā)現(xiàn)或?qū)⑼苿?dòng)維生素D制劑在肌肉萎縮防治中的精準(zhǔn)應(yīng)用，為全球約5億慢性病患者改善肌肉健康提供新策略。研究獲得泰國國家研究基金支持，所有作者聲明無利益沖突。
相關(guān)文獻(xiàn)：
1.Abiri, B. , & Vafa, M. (2020). Vitamin D and muscle sarcopenia in aging. Methods in Molecular Biology, 2138, 29–47. - PubMed
2.Aguilar‐Jimenez, W. , Villegas‐Ospina, S. , Gonzalez, S. , Zapata, W. , Saulle, I. , Garziano, M. , Biasin, M. , Clerici, M. , & Rugeles, M. T. (2016). Precursor forms of vitamin D reduce HIV‐1 infection in vitro. Journal of Acquired Immune Deficiency Syndromes, 73, 497–506. - PubMed
3.Ali, T. M. , Mehanna, O. M. , Elsaid, A. G. , & Askary, A. E. (2016). Effect of combination of angiotensin‐converting enzyme inhibitors and vitamin D receptor activators on cardiac oxidative stress in diabetic rats. The American Journal of the Medical Sciences, 352, 208–214. - PubMed
4.An, B. S. , Tavera‐Mendoza, L. E. , Dimitrov, V. , Wang, X. , Calderon, M. R. , Wang, H. J. , & White, J. H. (2010). Stimulation of Sirt1‐regulated FoxO protein function by the ligand‐bound vitamin D receptor. Molecular and Cellular Biology, 30, 4890–4900. - PMC - PubMed
5.Bodine, S. C. , & Baehr, L. M. (2014). Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin‐1. American Journal of Physiology, Endocrinology and Metabolism, 307, E469–E484. - PMC - PubMed
6.Brink, M. , Price, S. R. , Chrast, J. , Bailey, J. L. , Anwar, A. , Mitch, W. E. , & Delafontaine, P. (2001). Angiotensin II induces skeletal muscle wasting through enhanced protein degradation and down‐regulates autocrine insulin‐like growth factor I. Endocrinology, 142, 1489–1496. - PubMed
7.Chaffer, T. J. , Leduc‐Gaudet, J. P. , Moamer, A. , Broering, F. E. , Gouspillou, G. , & Hussain, S. N. A. (2021). Novel insights into the autonomous role played by vitamin D receptor in the regulation of skeletal muscle mass. The Journal of Physiology, 599, 1955–1956. - PubMed
8.Clarke, B. A. , Drujan, D. , Willis, M. S. , Murphy, L. O. , Corpina, R. A. , Burova, E. , Rakhilin, S. V. , Stitt, T. N. , Patterson, C. , Latres, E. , & Glass, D. J. (2007). The E3 ligase MuRF1 degrades myosin heavy chain protein in dexamethasone‐treated skeletal muscle. Cell Metabolism, 6, 376–385. - PubMed
9.Cohen, S. , Brault, J. J. , Gygi, S. P. , Glass, D. J. , Valenzuela, D. M. , Gartner, C. , Latres, E. , & Goldberg, A. L. (2009). During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1‐dependent ubiquitylation. The Journal of Cell Biology, 185, 1083–1095. - PMC - PubMed
10.Ferder, M. , Inserra, F. , Manucha, W. , & Ferder, L. (2013). The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin‐angiotensin system. American Journal of Physiology. Cell Physiology, 304, C1027–C1039. - PMC - PubMed
