5-羟色胺调控腰骶髓运动神经元钙离子通道在改善糖尿病大鼠尿道功能损害中的作用机制研究

糖尿病导致的尿道功能损害和腰骶髓运动神经元兴奋性改变有关，而细胞膜上的钙离子通道亚型（Cav1.2,Cav2.3,Cav3.2）可以影响神经元的兴奋性，推测糖尿病尿道功能损害可能和运动神经元钙离子通道改变相关。前期研究证实静脉给予5-HT1A及5-HT2A/2C受体激动剂可以改善糖尿病大鼠尿道功能，并发现腰骶髓控制尿道活动的运动神经元中5-HT2A和2C受体数量较正常大鼠明显增多，推测5-HT类物质通过和增多的5-HT受体特异性结合影响腰骶髓运动神经元的兴奋性，但对于糖尿病导致腰骶髓运动神经元靶向钙离子通道亚型改变，以及5-HT类物质如何通过调控靶向钙离子通道功能改善糖尿病大鼠尿道功能损害的作用机制还不清楚。本研究主要目的是阐明糖尿病导致腰骶髓运动神经元中靶向钙离子通道亚型改变，并探讨5-HT类物质调控靶向钙离子通道改善糖尿病大鼠尿道功能可能作用机制，为临床开发新药提供理论和实验依据。

The changes of neuron excitability in lumbosacral cord motoneurons are involved in diabetes mellitus(DM)-induced urethral dysfunction. The calcium channel subtypes, such as Cav1.2, Cav2.3, Cav3.2, are closely related to neuron excitability. Therefore, it is assumed that DM-induced urethral dysfunction may causes the changes of calcium channels in lumbosacral cord motoneurons. Previous studies have confirmed that intravenous injection of serotonin receptor agonist could improve the urethral dysfunction in DM rats, and discovered that number of serotonin receptors of motoneurons in lumbosacral cord controlling the external urethral sphincter in DM rats was significantly increased than normal rats, suggesting that the serotonin ligands could mainly bond with the compensatory increased serotonin receptors, and then improve neuron excitability in DM rats. Whereas the changes of calcium channels in lumbosacral cord motoneurons by DM and the regulatory mechanism of serotonin agonist have not been clarified. Our main purpose was to clarify the changes of calcium channel subtypes in lumbosacral motoneurons by DM, explore the mechanism of serotonin regulating calcium channel subtypes improving the urethral dysfunction simultaneously, and further provide the theoretical and experimental basis for the development of new drugs in clinics.