中枢5-羟色胺能神经元的可塑性改变在糖尿病大鼠排尿功能障碍中的作用机制研究

糖尿病可以并发周围和中枢神经病变，导致膀胱和尿道发生功能和形态学异常，从而引起排尿功能障碍。中枢5-羟色胺（5-HT）能神经元的可塑性改变与之密切相关，前期研究已经证实静脉给予5-HT类受体激动剂可以改善糖尿病大鼠的排尿障碍，并发现糖尿病大鼠腰骶髓控制尿道外括约肌活动的Onuf’s核中5-HT受体数量较正常明显增多；但和排尿密切相关的高位中枢，即前额皮质、下丘脑视前区、中脑导水管灰质、脑桥排尿中枢的5-HT能神经元的改变缺乏相关研究。推测糖尿病可能诱发高位中枢的5-HT神经元发生可塑性改变，而5-HT类药物可以通过特异性结合目标脑区内代偿性增多的5-HT类受体，改善糖尿病大鼠的排尿障碍。本研究主要目的是阐明目标脑区5-HT能神经元的可塑性改变在糖尿病大鼠排尿障碍中的作用，探讨5-HT类药物改善糖尿病大鼠排尿障碍的中枢作用机制，为临床开发新药提供理论和实验依据。

Diabetes mellitus (DM) can be complicated with peripheral and central neuropathy, causing the function and morphology change of the bladder and the urethra, which could lead to the urinary voiding dysfunction. Moreover, the change is closely related to the plasticity of central serotonin neuron. Previous studies have confirmed that intravenous injection of serotonin receptor agonist could improve the urinary voiding dysfunction in DM rats, and discovered that number of serotonin receptors of Onuf 's nuclear in lumbosacral cord controlling the external urethral sphincter in DM rats was significantly increased than normal rats. Whereas the plasticity changes of serotonin neurons in the high central nervous system have not been clarified, such as the prefrontal cortex, the hypothalamus, the periaqueductal gray and pontine micturition center. DM could induce a plasticity change in central serotonin neurons, and the serotonin ligands could mainly bond with the compensatory increased serotonin receptors, and then improve urination disorder in DM rats. Our main purpose was to clarify the role of the central serotonin neurons plasticity in the urinary voiding dysfunction in DM rats, explore the mechanism of the central serotonin improving the voiding dysfunction simultaneously, and further provide the theoretical and experimental basis for the development of new drugs in clinics.