顺铂是一线抗癌药，其耳毒性机制仍不明晰。前期研究中，我们发现顺铂可激活耳蜗细胞上瞬时感受器电位香草酸受体1（TRPV1），导致钙内流和钙超载，从而引发细胞凋亡。钙池操纵性钙通道（SOCC）是胞外钙内流的重要通道，基质交感分子1（STIM1）、Orail和TRPs 是构成SOCC的关键蛋白，三者间相互调控。我们发现给予顺铂后，STIM1、Orail和TRPV1的表达呈剂量依赖性升高，同时钙蛋白酶（calpain）的表达也明显增强，且与细胞凋亡率呈正相关。据此，我们推论STIM1/TRPV1/calpain通路可能参与了顺铂耳毒性过程。我们最新研究提示，葛根素作为中药制剂，可有效防护顺铂耳毒性，但其防护机制有待阐明。综上，本课题拟利用分子生物学、显微形态学及其它相关技术，研究STIM1/TRPV1/calpain通路在顺铂所致耳毒性中的作用及葛根素的防护机制，为临床防治药物性聋提供新途径。

Cisplatin is a highly effective anti-cancer drug that is widely used in clinic now.However, serious ototoxicity of cisplatin become an important factor affecting its use. At present, the mechanism of cisplatin ototoxicity is still unclear. Our previous study found that cisplatin could activate transient receptor potential vanilloid 1 (TRPV1) in cochlear cell, TRPV1 caused calcium influx and overload, which causing cochlear cell apoptosis finally. Store-operated calcium channels (SOCC) are important channels of the inflow of extracellular calcium, stromal interacting molecule (STIMI), Orail and transient receptor potentials (TRPs) are the keys to constitute the SOCC proteins, and they can modulate with each other. We found that after giving cisplatin, the expression of STIM1, Orail and TRPV1 is increased with a dose-effect relationship. At the same time, the expression of calcium protease enhanced obviously, which was positive correlated with cell apoptosis rate. On this basis, we deduce that STIM1 / TRPV1 / calpain pathway may be involved in cisplatin-induced ototoxicity. Our latest studies suggest that puerarin as Chinese native medicine preparation, can effectively protective cisplatin ototoxicity, but its protective mechanism is to be explored. This project intends to investigate the role of STIM1 / TRPV1 / calpain pathway in cisplatin ototoxicity and the protective mechanism of puerarin by using molecular biological, micromorphological and other techniques, so as to provide new route for clinical prevention and treatment of drug deafness.