Basical study for regulation of apoptosis; Aiming to improve the results and to enlarge the application of cochlear implant surgery.

尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）与细胞凋亡密切相关。我们发现uPAR在耳蜗中存在，尤其是在皮质器和螺旋神经节中，这表明uPA-uPAR抗凋亡系统在耳蜗中起作用。接下来，我们证明，使用大鼠耳蜗器官型培养物，uPA以剂量依赖性方式减弱氨基糖苷诱导的凋亡性毛细胞死亡。我们还证明了人工抗凋亡蛋白PTD-FNK通过影响caspase-9相关的线粒体凋亡途径来减弱氨基糖苷诱导的凋亡性毛细胞死亡。

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are recently shown to have close relationship to the apoptosis. We demonstrated that uPAR was in the cochlea especially in organ of corti and spiral ganglion, which is indicating that the uPA-uPAR anti-apoptotic system is working in cochlea. Next we demonstrated, using cochlear organotypic cultures of the rat, that uPA attenuates the aminoglicoside induced apoptotic hair cell death in a dose dependent manner. We have also demonstrated that artificial anti-apototic protein PTD-FNK attenuates the aminoglicoside induced apoptotic hair cell death by affecting caspase-9 related mitochondrial apoptotic pathway.