DO是临床最常见的逼尿肌兴奋性异常，严重影响患者生活质量。逼尿肌自发性兴奋异常增强是DO发生的关键环节，我们前期发现：CD38基因敲除可显著降低DO逼尿肌自发性兴奋，此效应可被cADPR拮抗剂逆转，提示CD38/cADPR信号通路异常可促进DO的发生，但其具体机制不清。RyR2是调控逼尿肌兴奋性的关键通道，我们既往研究发现：cADPR可通过影响结合在RyR2上的FKBP12.6数量，调控RyR2的开放；结合在RyR2上的FKBP12.6增加，导致RyR2开放下降是引起DO逼尿肌兴奋性增加的关键原因。据此，我们推测，CD38/cADPR信号异常可能通过调控RyR2上FKBP12.6数量，促进DO的发生。本研究拟从单细胞、逼尿肌条和在体膀胱3个层面，利用CD38和FKBP12.6基因敲除鼠，探讨CD38/cADPR信号异常促DO发生的分子机制及对信号通路干预用于治疗DO的效果。

Detrusor instability(DO) have a significant impact on quality of life. The increased excitability of detrusor is the key mechanism of myogenic basis associated with DO. But the mechanism remains largely unexplored. Using CD38 null mice as a model, we show that the abnormal increased excitability of detrusor was significantly reduced by CD38 KO. Our previous studies showed that impaired RyRs opening, which was related to the increased binding of FKBP12.6 to RyR2, was the key factor for the development of DO. cADPR plays a pivotal role in regulation of RyR2 channel by binding to FKBP12.6. Therefore, it is reasonable to hypothesis that alteration of CD38/cADPR signal may result in defective RyR2 open via FKBP12.6. Using CD38 and FKBP12.6 null mice, we sought to investigate the The mechamism and regulation effect of altered CD38/Cyclic ADP-Ribose signaling contributes to the DO.