Calpain 1在水杨酸钠诱导耳鸣大鼠的下丘脑神经元中的表达及对听力的影响

Expression of Calpain 1 in Hypothalamus Neurons of Tinnitus Rats Induced by Sodium Salicylate and Its Influence on Hearing

为了考察Calpain 1在水杨酸钠诱导耳鸣大鼠的下丘脑神经元中的表达及对听力的影响,本研究通过腹腔注射水杨酸钠建立耳鸣大鼠模型,并腹腔注射钙蛋白酶抑制剂ALLN来处理大鼠。听性脑干反应(ABR)测试显示,水杨酸钠可显著升高大鼠的的听力阈值和Ⅰ、Ⅲ和Ⅴ波潜伏期、Ⅰ~Ⅴ和Ⅲ~Ⅴ波间潜伏期,而钙蛋白酶抑制剂可明显抑制这种变化。免疫组化、RT-PCR和Western blotting检测结果均显示,水杨酸钠可明显上调大鼠下丘组织中Calpain 1的表达,而钙蛋白酶抑制剂可显著抑制Calpain 1的上调。此外,钙蛋白酶抑制剂可显著抑制水杨酸钠诱导的大鼠下丘组织中NMDA受体亚型NR2A的上调。水杨酸钠上调了大鼠耳蜗核组织中炎症因子TNF-α、IL-1β和IL-6的表达,而钙蛋白酶抑制剂可显著抑制炎症因子的表达。本研究提示,水杨酸钠可损伤大鼠的听觉功能,上调Calpain 1、NMDA受体和促炎细胞因子的表达。钙蛋白酶抑制剂可显著改善大鼠的听觉功能,其机制与抑制Calpain 1、NMDA受体和促炎细胞因子的表达有关。

To investigate the expression of Calpain 1 in hypothalamic neurons induced by sodium salicylate in rats and its effect on hearing, in this study, a rat model of tinnitus was established by intraperitoneal injection of sodium salicylate, and rats were treated with intraperitoneal injection of calpain inhibitor ALLN. Auditory brainstem response(ABR) tests showed that sodium salicylate significantly increased the hearing threshold andⅠ,ⅢandⅤwave latency,Ⅰ~ⅤandⅢ~Ⅴwave latency, while calpain inhibitors significantly inhibited this change. The results of immunohistochemistry, RT-PCR and Western blotting showed that sodium salicylate could up-regulate the expression of Calpain 1 in rat inferior colliculus, and calpain inhibitor could significantly inhibit the up-regulation of Calpain 1. In addition, calpain inhibitors significantly inhibited the up-regulation of NMDA receptor subtype NR2 A in rat hypothalamic tissue induced by sodium salicylate. Sodium salicylate up-regulated the expression of inflammatory factors TNF-α, IL-1β and IL-6 in rat cochlear nucleus, while calpain inhibitor significantly inhibited the expression of inflammatory factors. This study suggests that sodium salicylate can impair the auditory function of rats and up-regulate the expression of Calpain 1, NMDA receptors and pro-inflammatory cytokines. Calpain inhibitors can significantly improve the auditory function of rats, and its mechanism is related to the inhibition of the expression of Calpain 1, NMDA receptors and pro-inflammatory cytokines.