Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China; Department of Otorhinolaryngology, West China Hospital, Sichuan University, Chengdu, China.
Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
Exp Neurol. 2014 Apr;254:216-23. doi: 10.1016/j.expneurol.2013.12.014. Epub 2013 Dec 29.
No effective medication for hyperbilirubinemia yet exists. Taurine is believed to exert a neuroprotective action. The aim of the present study was to determine whether taurine protected neurons of the rat anteroventral cochlear nucleus (AVCN) against bilirubin-induced neuronal hyperexcitation. AVCN neurons were isolated from 13 to 15-day-old Sprague-Dawley rats. The effects of bilirubin on the spontaneous excitatory postsynaptic currents (sEPSCs) and action potential currents were compared with those exerted by bilirubin and taurine together. Bilirubin dramatically increased the frequencies of sEPSCs and action potential currents, but not sEPSC amplitude. Taurine suppressed the enhanced frequency of action potentials induced by bilirubin, in a dose-dependent manner. In addition, taurine decreased the amplitude of voltage-dependent calcium channel currents that were enhanced upon addition of bilirubin. We explored the mechanism of the protective effects exerted by taurine using GABAA and glycine receptor antagonists, bicuculline and strychnine, respectively. Addition of bicuculline and strychnine eliminated the protective effects of taurine. Neither bilirubin nor taurine affected the sensitivity of the glutamate receptor. Our findings thus indicate that taurine protected AVCN neurons against bilirubin-induced neuronal hyperexcitation by activating the GABAA and glycine receptors and inhibiting calcium flow through voltage-gated channels. Thus, taurine may be effective in treatment of neonatal hyperbilirubinemia.
目前尚无针对高胆红素血症的有效药物。牛磺酸被认为具有神经保护作用。本研究旨在确定牛磺酸是否能保护大鼠前腹耳蜗核（AVCN）神经元免受胆红素诱导的神经元过度兴奋。从 13 至 15 天大的 Sprague-Dawley 大鼠中分离 AVCN 神经元。比较了胆红素对自发性兴奋性突触后电流（sEPSC）和动作电位电流的影响，以及胆红素和牛磺酸共同作用的影响。胆红素显著增加了 sEPSC 和动作电位电流的频率，但不增加 sEPSC 幅度。牛磺酸以剂量依赖的方式抑制了胆红素诱导的动作电位频率的增强。此外，牛磺酸降低了电压依赖性钙通道电流的幅度，而胆红素增加了钙通道电流的幅度。我们使用 GABAA 和甘氨酸受体拮抗剂，即印防己毒素和士的宁，分别探讨了牛磺酸保护作用的机制。加入印防己毒素和士的宁消除了牛磺酸的保护作用。胆红素和牛磺酸均不影响谷氨酸受体的敏感性。因此，我们的研究结果表明，牛磺酸通过激活 GABAA 和甘氨酸受体以及抑制电压门控通道中的钙流来保护 AVCN 神经元免受胆红素诱导的神经元过度兴奋。因此，牛磺酸可能对新生儿高胆红素血症的治疗有效。
