雷公藤甲素对2型糖尿病小鼠耳蜗毛细胞的保护作用

目的：探讨雷公藤甲素对2 型糖尿病小鼠耳蜗毛细胞的保护作用及机制。方法：选取 Balb/c 雄性小鼠，随 机分为正常组、糖尿病组和雷公藤甲素组。制备2 型糖尿病小鼠模型后，雷公藤甲素组给予雷公藤甲素0.1 mg/kg 灌胃，正常组和糖尿病组小鼠均给予等体积生理盐水灌胃。观察3 组小鼠耳蜗毛细胞的变化，检测耳蜗毛细胞内 氧化应激相关信号通路、抗氧化蛋白及凋亡分子的表达变化。结果：糖尿病组和雷公藤甲素组耳蜗毛细胞均有不 同程度的丢失，且雷公藤甲素组耳蜗毛细胞的丢失率小于糖尿病组。雷公藤甲素组小鼠耳蜗毛细胞中的p-ERK、 E2 核因子相关因子2（Nrf2）、硫氧还蛋白（Trx）表达量及Erk 磷酸化水平高于糖尿病组， JNK磷酸化水平和凋 亡分子cleaved-caspase-3 的蛋白表达量低于糖尿病组。结论：雷公藤甲素可以减缓糖尿病小鼠耳蜗毛细胞凋亡， 其机制与上调ERK、Nrf2 和Trx 的表达，下调JNK信号，抑制凋亡分子cleaved-caspase-3 的表达有关，有望成为 治疗2 型糖尿病耳蜗病变的有效药物。

Protective effect of triptolide on cochlea hair cells in type 2 diabetic mice

Objective To discuss the protective effect and mechanism of triptolide on cochlea hair cells in diabetic mice. Methods Male Balb/c mice were randomly divided into control， diabets and triptolide group．Diabetic mice models were established and then triptolide group was lavaged with 0.1 mg/kg triptolide， while the control group and diabetes group were lavaged with the same volume of physiological saline. Among three groups， changes of hair cells in the cochlea were observed and expression of antioxidant and apoptosis protein within cochlea hair cells was detected. Results The loss of cochlea hair cells in diabets and triptolide groups were more than that in control group， and the loss of cochlea hair cells in triptolide group was less than that in diabets group. In triptolide group， antioxidant molecule protein expression of p-ERK， Nrf2 and Trx in cochlea hair cells was significantly higher， while expression of p-JNK and cleaved-caspase-3 was significantly lower than those in diabets group．Conclusion Triptolide can slow the apoptosis of cochlea hair cells in diabetic mice， which is related to the increased expression of p-ERK， Nrf2 and Trx protein and decreased expression of p-JNK and cleaved-caspase-3， and therefore it is expected to become an effective drug for treatment of diabetic cochlea disease.