钩藤碱调控T型钙通道抑制骶髓上损伤膀胱Cajal间质细胞兴奋性及分子机理研究

Suprasacral cord injury（SSCI）can cause the detrusor hyperreflexia, dysuresia, and urinary reservoir dysfunction. In our previous study, the Cx43 expression on the bladder Cajal mesenchymal cells (ICC) was increased upon the reflex excitement of detrusor muscle, which was inhibited by rhynchophylline. Rhynchophylline inhibited the detrusor hyperreflexia, decreased Cx43 expression, and protected the bladder compliance. The effects of rhynchophylline on the bladder compliance might not be explained by its regulation of type L calcium channel on ICC cells. Therefore, we hypothesize that rhynchophylline can suppress the excitement of bladder tissue ICC, normalize the smooth muscle pacing, and improve the function of detrusor muscle via modulating the type T calcium channel of ICC cells. Here, we will investigate the effects of rhynchophylline on the excitation of post-SSCI detrusor reflex and ICC cells using the neurogenic bladder model of SSCI and cell culture of ICC. The regulatory effects of rhynchophylline on the type T calcium channel current are being studied and the molecular mechanisms are going to be explored about the improvement of detrusor function in post-SSCI neurogenic bladder. We also plan to clarify the effects and mechanisms of rhynchophylline on post-SSC bladder dysfunction. If successful, the study will be helpful to enrich the pathogenesis of nervous bladder and to treat the post-SSCI neurogenic bladder.

骶髓上损伤（SSCI）会导致逼尿肌反射亢进，引起膀胱排尿、贮尿功能障碍。前期研究发现逼尿肌反射亢进时，膀胱Cajal间质细胞（ICC）表面上的平滑肌结构蛋白Cx43表达增加，钩藤碱能通过调控L型钙通道抑制膀胱逼尿肌收缩并降低Cx43表达，同时还对膀胱顺应性有明显保护作用，然而单纯用钩藤碱调控ICC上L型钙通道无法解释膀胱顺应性的变化。为此，我们提出假说：钩藤碱可能通过调控ICC 细胞的T型钙通道，抑制SSCI膀胱ICC细胞兴奋性，改善膀胱逼尿肌功能。本项目拟采用SSCI大鼠神经源性膀胱模型和体外ICC细胞培养，研究钩藤碱对SSCI后逼尿肌反射亢进和ICC细胞兴奋性的作用，探讨钩藤碱调控逼尿肌ICC细胞T型钙通道电流，改善SSCI后神经源性膀胱逼尿肌功能的分子机理，阐明钩藤碱干预对SSCI后膀胱功能障碍的作用及机制，为治疗SSCI后神经源性膀胱提供新的理论依据和实验基础。