缩泉丸对糖尿病膀胱神经传导功能异常的修复作用及其机制研究

糖尿病膀胱（DCP）是一种常见的糖尿病并发症。在前期研究工作中发现，补肾缩尿的代表方缩泉丸通过调节膀胱平滑肌上相关神经受体的表达从而调节平滑肌运动，临床和预实验研究中均证明缩泉丸对DCP有治疗作用。我们与哈佛大学合作的前期研究中发现：肌球蛋白Myosin Va 在膀胱神经元突触递质释放中起重要作用，课题组提出“缩泉丸通过调控Myosin Ⅴa参与运动神经元递质释放、调节膀胱神经传导功能，发挥治疗DCP的作用。”的假说。本项目利用整体观察比较和CRISPR-Cas9基因敲除等最新技术方法，从整体、组织、细胞和分子水平系统探讨：（1）DCP 膀胱神经传导的异常及Myosin Va调节膀胱运动神经传导的分子信号通路机制;（2）缩泉丸对DCP模型动物膀胱神经传导的影响及其对Myosin Va 的基因转录与蛋白表达的调控作用，目的是阐明缩泉丸治疗DCP 的分子机制，丰富中医补肾缩尿理论的内涵。

Diabetic Cystopathy (DCP) is one of most common complications in diabetes. Suo Quanwan(SQW), as a main prescription of TCM therapy “nourishing kidney and reducing urination”, regulates the expression of neurotransmitters of bladder smooth muscle. Based on the Clinical researches, SWQ has significant effect on the treatment of DCP. By the workshop with Harvard Medical School, it is proved that Myosin Va plays an important role in the presynaptic release of neurotransmitters in bladder neurons. So we proposed the hypothesis that the mechanism of SQW in the treatment of DCP is related to its regulation of neurotransmitter release via myosin Va. By means of CRISPR-Cas9 gene editing technique, we will investigate (1) the abnormality of neurotransmission in DCP animal and potential signaling pathway regulated via Myosin Va. (2) the influence of SQW on such abnormal neurotransmission and regulation on the transcription and expression of the gene of Myosin Va. Our aim is to eluciates the underlying mechanism of SQW in the treatment of DCP, which could enrich our knowledge on the theory of Kidney improvement in TCM.