Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity.
Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity.
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p47phox 的激活是布比卡因诱导活性氧爆发和神经毒性的机制。
DOI：
10.1155/2017/8539026
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发表时间：
2017
影响因子：
--
通讯作者：
Xu SY
中科院分区：
文献类型：
--
作者：
Li YJ;Zhao W;Yu XJ;Li FX;Liu ZT;Li L;Xu SY
布比卡因可通过诱导过量活性氧（ROS）而引起神经毒性，但其机制尚不清楚。NOX 2是神经系统中最重要的ROS来源之一，其激活需要亚基p47 phox的膜转位。然而，p47 phox在布比卡因诱导的神经毒性中的作用尚未探讨。在我们的体外研究中，培养的人SH-SY 5 Y神经母细胞瘤细胞用1.5 mM布比卡因处理以诱导神经毒性。通过测量p47 phox的胞质/膜比率来评估p47 phox的膜易位。研究了NOX抑制剂VAS 2870和p47 phox-siRNA对布比卡因诱导的神经毒性的影响。此外，在大鼠体内评估了VAS 2870对布比卡因诱导的神经毒性的影响。这些变化可通过VAS 2870预处理或p47 phox-siRNA转染SH-SY 5 Y细胞而逆转。同样，用VAS 2870预处理可减弱大鼠中布比卡因诱导的神经元毒性。结论：增强p47 phox膜转位是布比卡因诱导神经毒性的主要机制，预先用VAS 2870或局部p47 phox基因敲减布比卡因诱导的神经细胞损伤。
Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury.