经皮电刺激对失神经支配后肌纤维微结构及力学性能影响的研究

项目名称： 经皮电刺激对失神经支配后肌纤维微结构及力学性能影响的研究

项目编号： No.11472018

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 周谋望

作者单位： 北京大学

项目金额： 95万元

中文摘要： 经皮电刺激用于肌肉失神经支配的治疗，可防治肌肉萎缩，保持肌肉活性。但其机制不明，对肌纤维的微结构及力学性能的影响尚无报道。肌纤维力学性能与自身纤维类型及其结构亚单位肌原纤维的微结构直接相关。Dystropgin是肌原纤维中的重要细胞骨架蛋白，对维持肌原纤维微结构稳定及肌纤维力学性能不可或缺，该蛋白表达受Akt信号通路调控。本项目在前期工作基础上，拟研究失神经支配肌肉接受经皮电刺激后，单根肌纤维力学性能的变化及其肌原纤维微结构的改变，分析二者改变与Dystrophin含量的相关性。再进一步从细胞水平研究在电刺激影响肌纤维Dystrophin表达和肌原纤维微结构过程中，细胞Akt信号通路发挥的作用。最终建立信号通路-细胞骨架蛋白-肌原纤维微结构-肌纤维力学性能的内在本质联系，并探讨不同类型肌纤维在电刺激下的力学响应，对揭示经皮电刺激治疗肌肉失神经支配的作用机制具有重大意义。

中文关键词： 肌纤维；失神经支配；经皮电刺激；微结构；力学性能

英文摘要： Electrical stimulation is a widely-used therapy for patients with muscle denervation. Several researches have revealed that electrical stimulation inhibited muscle atrophy and reserved muscle activity. But the underlying mechanisms remain uncertain. Up to now, there is no report focusing on the microstructure and mechanical property of myofibers after denervation and electrical stimulation. The mechanical property of a myofiber depends on its fiber type and the microstructure of myofibril.Dystrophin is a kind of cytoskeleton protein in the myofibril, and plays an important role in maintaining the stability of myofibril microstructure and mechanical property of myofiber. Expression of Dystrophin is regulated by the Akt pathway. In the present study, we plan to investigate the probable changes in the microstructure and mechanical property of single denervated myofiber after electrical stimulation, and their correlation with the changes of Dystrophin expression. Furthermore, we will also investigate the role of Akt pathway during a series of changes in myofiber structure and property induced by electrical stimulation. Our aim is to reveal the internal interaction of biological signal pathway-cytoskeleton protein-microstructure-mechanicssystem, and to discuss the different responses of three different myofiber types to the electrical stimulation.These will provide important evidences to explain the mechanisms underlying the theuraputic effects of electrical stimulation on the denervated muscles.

英文关键词： myofiber;denervation;electrical stimulation;microstructure;mechanical property