骶上脊髓完全性损伤后神经源性膀胱的光修复

项目名称： 骶上脊髓完全性损伤后神经源性膀胱的光修复

项目编号： No.81200960

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 张志成

作者单位： 中国人民解放军北京军区总医院

项目金额： 23万元

中文摘要： 脊髓损伤后排尿功能障碍是晚期患者死亡的主要原因。骶上脊髓损伤所致神经源性膀胱临床较常见，既往治疗措施如间歇导尿、药物、常规手术等效果欠佳且存在一定不足。骶神经前根电刺激联合后根切断去传入虽获得广泛应用和较好效果，但仍有问题无法克服，如刺激器故障导致失败、异物长期植入并发症、前根刺激引发躯体不适、费用较高等。光感基因ChR2编码胞膜阳离子通道蛋白，蓝光照射可引起通道开放致阳离子内流，引发细胞兴奋。因此，本研究拟将ChR2基因转染骶上脊髓完全性损伤大鼠骶髓内支配膀胱逼尿肌运动的骶副交感核，使其表达ChR2通道，同时行骶神经后根切断去传入抑制逼尿肌过度反射及逼尿肌/尿道外括约肌协同失调，骶髓行蓝光照射，利用光感基因活化技术选择性刺激支配膀胱逼尿肌的骶副交感核产生兴奋，引起膀胱逼尿肌收缩，促进逼尿肌/括约肌协调，从而修复排尿功能，以期为骶上脊髓完全性损伤后神经源性膀胱的功能重建提供一种崭新的思路。

中文关键词： 脊髓损伤；神经源性膀胱；光感基因技术；骶神经前根电刺激；功能重建

英文摘要： Urinary dysfunction after spinal cord injury is the main reason of advance patient death. Neurogenic bladder resulted from supersacral spinal cord injury is very common in clinical practice. The effects of previous treatment measures such as intermittent catheterization, medication, conventional surgery were not good enough and had some problems. Sacral anterior root electrical stimulation with sacral posterior root deafferentation have been widely used and obtained good results. There are still some problems, which cannot be overcome, such as stimulator fault resulting in treatment failure, complications of long-term foreign body implantation, physical discomfort caused by sacral nerve root stimulation, higher cost, etc. Light-sensitive gene ChR2 encodes cell membrane cationic channel protein which could be activated by photostimulation of blue light. Activated ChR2 cationic channel protein may open and result in cations internal flow that could lead to cell action potential and excitation. Therefore, this study intends to transfect sacral parasympathetic nucleus which dominate movement of bladder detrusor in sacral cord of complete supersacral spinal cord injury rats with light-sensitive gene ChR2. At the same time, sacral posterior root deafferentation will be performed to release detrusor excessive reflectio

英文关键词： spinal cord injury；Neurogenic bladder；Optogenetic techology；Sacral anterior root stimulation；Functional reconstruction