日本研究小組在利用小鼠進行的實驗中發(fā)現(xiàn),，通過遏制一種基因的作用,，能改善肌肉萎縮的癥狀。
德島大學教授田中榮二率領的研究小組發(fā)現(xiàn),，myostatin基因會抑制骨骼肌的增加,。于是他們利用ＲＮＡ干擾法，抑制該基因發(fā)揮作用,。研究人員確認,，經(jīng)ＲＮＡ干擾法治療，患肌肉萎縮癥小鼠的顎部骨骼肌的肌肉量增加,，咬力也得到增強,。
田中榮二指出，目前治療肌肉萎縮癥主要是通過康復療法等抑制肌肉萎縮,，而利用此次成果有望開發(fā)出促進肌肉量增加的新療法。
據(jù)介紹,，小鼠每接受一次注射,，效果能夠持續(xù)４周左右，而要想改善肌肉萎縮癥患者的癥狀,，需要大劑量注射,。研究小組準備開發(fā)能廉價注射的方法，爭取早日用于臨床,。
相關論文已發(fā)表在5月23日一期的美國在線科學雜志《科學公共圖書館—綜合》PLoS ONE上,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0064719
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Local Applications of Myostatin-siRNA with Atelocollagen Increase Skeletal Muscle Mass and Recovery of Muscle Function
Emi Kawakami, Nobuhiko Kawai, Nao Kinouchi, Hiroyo Mori, Yutaka Ohsawa, Naozumi Ishimaru, Yoshihide Sunada, Sumihare Noji, Eiji Tanaka mail
Background Growing evidence suggests that small-interfering RNA (siRNA) can promote gene silencing in mammalian cells without induction of interferon synthesis or nonspecific gene suppression. Recently, a number of highly specific siRNAs targeted against disease-causing or disease-promoting genes have been developed. In this study, we evaluate the effectiveness of atelocollagen (ATCOL)-mediated application of siRNA targeting myostatin (Mst), a negative regulator of skeletal muscle growth, into skeletal muscles of muscular dystrophy model mice. Methods and Findings We injected a nanoparticle complex containing myostatin-siRNA and ATCOL (Mst-siRNA/ATCOL) into the masseter muscles of mutant caveolin-3 transgenic (mCAV-3Tg) mice, an animal model for muscular dystrophy. Scrambled (scr) -siRNA/ATCOL complex was injected into the contralateral muscles as a control. Two weeks after injection, the masseter muscles were dissected for histometric analyses. To investigate changes in masseter muscle activity by local administration of Mst-siRNA/ATCOL complex, mouse masseter electromyography (EMG) was measured throughout the experimental period via telemetry. After local application of the Mst-siRNA/ATCOL complex, masseter muscles were enlarged, while no significant change was observed on the contralateral side. Histological analysis showed that myofibrils of masseter muscles treated with the Mst-siRNA/ATCOL complex were significantly larger than those of the control side. Real-time PCR analysis revealed a significant downregulation of Mst expression in the treated masseters of mCAV-3Tg mice. In addition, expression of myogenic transcription factors was upregulated in the Mst-siRNA-treated masseter muscle, while expression of adipogenic transcription factors was significantly downregulated. EMG results indicate that masseter muscle activity in mCAV-3Tg mice was increased by local administration of the Mst-siRNA/ATCOL complex. Conclusion These data suggest local administration of Mst-siRNA/ATCOL complex could lead to skeletal muscle hypertrophy and recovery of motor disability in mCAV-3Tg mice. Therefore, ATCOL-mediated application of siRNA is a potential tool for therapeutic use in muscular atrophy diseases.
