Cajal样间质细胞调控Oddi括约肌运动及在Oddi括约肌功能障碍发病中的作用研究

Sphincter of Oddi dysfunction(SOD) is a functional disorder with hypermotility of sphincter of Oddi(SO) being its main characteristic. Up to now, the underlying mechanism of SOD remains unclear and there is still no specified drug therapy target for this disorder in clinic. Combined the previous study results, this study follows the clue that hypermotility of SO in SOD and the morphological evidence of the presence of interstitial Cajal-like cells(ICLCs) in SO to discuss the role of ICLCs in the contrl of SO motility and the pathogenesis of SOD. Immunohistofluorescence, transmission electrical microscope, laser confocal microscope calcium flash and calcium wave recording technique, reverse transcription polymerase reaction and protein chromatography are to be used to analyze the quantitative and function changes of ICLCs in SO and the changes in c-kit and stem cell factor(SCF) gene expression occurring in SOD patients. Changes of SO motility when c-kit pathway is blocked by ACK-II will also be observed. Understanding the role of ICLCs in the control of SO motility and pathogenesis of SOD will provide new therapeutic target and new theoretical evidence for the treatment of SOD in clinic.

Oddi括约肌功能障碍（SOD）属于功能性动力紊乱，Oddi括约肌（SO）张力增高是其主要表现，但其机理尚不清楚，因而临床上对其的药物治疗靶点不明确。本课题以SOD中SO张力增高的现象为线索，以SO中存在Cajal样间质细胞（ICLCs）的形态学证据为基础，结合前期研究成果，从正常SO入手，探讨ICLCs在调控SO运动以及在SOD发病机理中的作用。本课题拟利用免疫组织荧光染色法、透射电镜技术、激光共聚焦显微镜钙离子闪光及钙离子流成像技术、逆转录聚合酶连反应法、蛋白印迹法等手段研究SO中ICLCs的形态学特征以及其在调控SO运动中的作用，同时研究SOD情况下SO中ICLCs数量及功能的变化，以及c-kit及scf基因表达的变化，并观察阻断c-kit通路后SO压力的变化。揭示ICLCs在调控SO运动以及在SOD发病中的作用，寻找SOD治疗靶点，为治疗SOD提供新的理论依据。