糖尿病膀胱功能障碍的病理机制及相关干预因素的研究

Diabetic bladder dysfunction (DBD), a collective description of clinical symptoms including decreased sensation, increased capacity, poor emptying, and also detrusor overactivity, is among the most common and costly complications of diabetes mellitus (DM). It is estimated that DBD occurs in approximately 87% of individuals diagnosed with DM, and substantially affects quality of life. Yet, little is known about the pathogenic mechanisms of DBD. Unlike other organs, the bladder experiences not only hyperglycemia, but also an increased volume of urine in DM . To aid in our knowledge of the pathophysiology of DBD and to aid development of specific treatments, identification of individual contributions of polyuria and hyperglycemia in the DBD is essential. .Based on the our previous research, we theorize that: diabetic cystopathy is a time-dependent disease in which diabetes and its associated diuresis causes temporal sensory abnormalities that result in an elevated threshold for initiating the micturition reflex and an increase in bladder capacity in the early stage of the disease. Distended bladder subsequently trigger compensated responses including bladder hypertrophy, the change of production or transfer of neurotransmitters and/or the change of the postjunctional receptors, and the change of the contractile apparatus. These changes are all beneficial for maintaining bladder function during the early stage of the disease and present as storage bladder dysfunction. In the late stage of diabetes, the accumulative effects of hyperglycemia through oxidative stress products lead to detrusor myogenic decompensation and polyneuropathy, causing the voiding bladder dysfunction with inability to empty representing the classical diabetic bladder dysfunction symptoms. We hypothesize further that treat DM rats with insulin and neotrophin will stop or slow the progress of DBD by control the blood glucose level or improve the neurofiber in bladder, therefor DBD maybe reversed within certain time frame.With our research, we can learn more about the pathophysiology mechanism of ROS and DBD,and that may help us find a therapeutic target to treat DBD.

糖尿病膀胱功能障碍(DBD)是糖尿病并发症中最常见、耗费最多的并发症之一。据估计单独诊断为糖尿病的患者中有87%会发生糖尿病下尿路并发症，严重影响患者的生活质量。但是我们对DBD的发病机制了解不充分，导致其目前发病率高而治疗手段有限的现状。我们的前期研究发现，糖尿病时多尿和高血糖共同作用于膀胱参与DBD的发病，多尿可以引起DBD早期的代偿性膀胱肥大，而慢性高血糖症引起的氧胁迫在DBD晚期膀胱衰竭中起重要作用。本研究通过建立糖尿病状态下尿流改道大鼠动物模型，并用胰岛素及神经营养因子对其进行干预，明确控制血糖及恢复神经功能对糖尿病膀胱功能障碍的影响及最佳干预时机。同时观察此状态是否可导致DBD失代偿期推迟出现或失代偿发生减轻。通过本研究可以使我们加强对高血糖症导致的高氧化应激状态与糖尿病膀胱功能障碍间病理生理学关系的认识，有助于研发新的治疗方法。

本研究针对糖尿病膀胱功能障碍(DBD)这一糖尿病并发症中最常见、耗费最多的并发症发病机制及影响因素进行研究。我们的前期研究发现，糖尿病时多尿和高血糖共同作用于膀胱参与DBD的发病，多尿可以引起DBD早期的代偿性膀胱肥大，而慢性高血糖症引起的氧胁迫在DBD晚期膀胱衰竭中起重要作用。本研究通过建立糖尿病大鼠及小鼠动物模型，并用胰岛素对大鼠模型进行干预，明确控制血糖对大鼠早期糖尿病膀胱功能障碍的逆转及最佳干预时机。渗透压相关的多尿是引起糖尿病早期膀胱功能和形态学上快速代偿性改变的主要原因，而这些改变至少在早期是可以被逆转的。通过本研究可以使我们加强对高血糖症导致的高氧化应激状态与糖尿病膀胱功能障碍间病理生理学关系的认识，有助于研发新的治疗方法。