氧化应激是噪音性聋的重要发生机制，Ca2+超载可能是噪音引起氧化应激反应的启动信号，而T-Ca2+通道可以维持细胞Ca2+稳态，还能参与调控氧化应激相关因子活性如FOXO3a，FOXO3a则是细胞氧化应激相关通路的下游因子之一。我们前期研究发现汉方己甲素(TET)能够保护噪音性聋，并且该药物能通过T-Ca2+通道降低Ca2+流，因此我们推测在拮抗噪音性聋的过程中，TET可能通过阻断T-Ca2+通道减少Ca2+内流，导致相关因子的活性抑制或激活，进一步激活并上调转录因子FOXO3a，减少ROS的产生。基于该假说我们建立了噪音性聋小鼠模型和运用RNA干扰技术将siRAN导入耳蜗沉默同源小鼠FOXO3a基因表达后的噪音性聋模型，通过听力学、形态学、分子学等手段探讨TET是否通过阻断T-Ca2+通道调控相关因子，并依赖FOXO3a的表达达到拮抗噪音性聋的作用，为临床噪音性聋的药物治疗提供实验依据。

Oxidative stress is an important mechanism of noise-induced hearing loss (NIHL), and Ca2+ overload may be its initiating signal. As one kind of calcium channels to maintain Ca2+ homeostasis, T-Ca2+ channels may also play an important role in regulating factors involved in oxidative stress, such as FOXO3a, which is one of the downstream factors in oxidative stress related pathways. In the preliminary study , We have found that Tetrandrine(TET) has an otoprotective effect against NIHL on CBA/CaJ mice. Besides, we found it could block T-Ca2+ channels on spiral ganglions. Thereby, we speculate that TET may reduce the generation of ROS by blocking T-Ca2+ channels, regulating the activation of CaN, AKT, AMPK and FOXO3a in the process of otoprotective effects. Based on this hypothesis, we will establish NIHL models on CBA/Ca mice and FOXO3a silenced CBA/Ca mice by injecting siRNA through round window. And we will use functional hearing test, morphology and molecular research methods to explore whether TET inhibits oxidative stress in NIHL relying on FOXO3a expression. So clarifying its mechanism against NIHL will supply an experiment evidence for the medicine from laboratory bench to bedside.