肉毒毒素A（BT-A）是局限性肌张力障碍的首选治疗，但单次注射后疗效持续时间有限。既往研究提示BT-A作用衰退与注射部位代偿性神经芽生有关。我们前期研究发现腓肠肌局部注射BT-A后，肌力恢复过程中局部新生神经肌肉接头形成并伴有肌肉特异性酪氨酸激酶（MuSK）表达上调；多种抑制神经芽生方法均可导致肌力恢复速度减慢，伴有新生神经肌肉接头形成减少及MuSK表达上调幅度减低。这些结果提示MuSK是调控代偿性神经肌肉接头形成及BT-A作用衰退的关键环节。本研究将探讨采用RNA干扰MuSK表达后，对BT-A注射后神经肌肉接头形成的影响，检测MuSK下游因子在动物及细胞水平的表达变化；通过补救实验探讨MuSK-Rac-PAK1通路和MuSK-Rac-GABP通路对乙酰胆碱受体基因表达及聚集的影响，阐明MuSK在BT-A作用后神经肌肉接头代偿性增生过程中的分子机制，为延长BT-A作用时效提供潜在干预靶点。

Botulinum toxin type A (BT-A) has become the preferred treatment for most kinds of focal dystonias, but the effective duration of a single injection is limited. The recession of BT-A’s effect has been reported to be related with nerve sprouting at injection site. Our previous study revealed new neuromuscular junction formation during the muscle strength recovery , which was accompanied with upregulated expression of the muscle specific tyrosine kinase (MuSK). Inhibition of the nerve sprouting caused by BT-A with different methods slowed the recovery of gastrocnemius muscle strength,which was accompanied with a reduction of new neuromuscular junction formation and less upregulation of MuSK. These results suggest that MuSK is a key point in new neuromuscular junction formation and BT-A effect recession. In this project , RNA interference technology will be used to interfere MuSK expression in individual and cellular levels. After the injection of BT-A, we will observe the formation of neuromuscular junction as well as the expressions of MuSK downstream factors. In order to clarify the molecular mechanisms of MuSK in the formation of neuromuscular junction, the role of MuSK-Rac-PAK1 pathway and MuSK-Rac-GABP pathway on acetylcholine receptor gene expression and clustering will be studied.To the results of this study will provide potential targets for intervention that can prolong the effective duration of BT-A .