Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine.
Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine.
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两种局部麻醉药的神经毒性比较：酰胺布比卡因与酯普鲁卡因
DOI：
10.1038/srep45316
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发表时间：
2017-03-24
影响因子：
4.6
通讯作者：
Xu SY
中科院分区：
文献类型：
--
作者：
Yu XJ;Zhao W;Li YJ;Li FX;Liu ZJ;Xu HL;Lai LY;Xu R;Xu SY
局部麻醉剂（LA）可能会导致神经系统并发症，但其潜在机制仍不清楚。许多神经毒性研究检查了不同的局麻药，但没有一个全面探讨酰胺型（布比卡因）和酯型（普鲁卡因）局麻药引起神经毒性的不同机制。在这里，基于 CCK8 测定、LDH 测定、Rhod-2-AM 和 JC-1 染色、2',7'-二氯氢荧光素二乙酸酯和二氢乙锭探针、碱性彗星测定和细胞凋亡测定，我们表明布比卡因和普鲁卡因均显着诱导线粒体钙超载和线粒体钙超载下降。 线粒体膜电位以及 ROS 过量产生、DNA 损伤和细胞凋亡 (P < 0.05)。布比卡因和普鲁卡因亚组间线粒体损伤和细胞凋亡差异无统计学意义（P > 0.05）。然而，令我们惊讶的是，布比卡因治疗后的超氧阴离子水平高于普鲁卡因治疗后的水平，这会导致更严重的DNA损伤，而普鲁卡因比布比卡因产生更多的过氧化反应。其中一些结果也在 C57 小鼠的背根神经节神经元中得到了证实。这些药物诱导的超氧化和过氧化的差异表明，不同类型的局麻药可能通过不同的途径引起神经毒性。我们可以根据其不同的神经毒性机制进行更精准的治疗。
Local anaesthetics (LAs) may lead to neurological complications, but the underlying mechanism is still unclear. Many neurotoxicity research studies have examined different LAs, but none have comprehensively explored the distinct mechanisms of neurotoxicity caused by amide- (bupivacaine) and ester- (procaine) type LAs. Here, based on a CCK8 assay, LDH assay, Rhod-2-AM and JC-1 staining, 2′,7′-dichlorohy-drofluorescein diacetate and dihydroethidium probes, an alkaline comet assay, and apoptosis assay, we show that both bupivacaine and procaine significantly induce mitochondrial calcium overload and a decline in the mitochondrial membrane potential as well as overproduction of ROS, DNA damage and apoptosis (P < 0.05). There were no significant differences in mitochondrial injury and apoptosis between the bupivacaine and procaine subgroups (P > 0.05). However, to our surprise, the superoxide anionic level after treatment with bupivacaine, which leads to more severe DNA damage, was higher than the level after treatment with procaine, while procaine produced more peroxidation than bupivacaine. Some of these results were also affirmed in dorsal root ganglia neurons of C57 mice. The differences in the superoxidation and peroxidation induced by these agents suggest that different types of LAs may cause neurotoxicity via different pathways. We can target more accurate treatment based on their different mechanisms of neurotoxicity.