Effects of anesthesia related drugs on neuronal apoptosis : alterations of enzymatic activities elicited by intracellular calcium elevation.

局麻药损伤神经元形态，干扰生理性神经传导。特别是在市售的局麻药中，利多卡因和丁卡因毒性最大。细胞凋亡是神经毒性的基本机制之一，然而，最近的文献报道，细胞凋亡并不能完全解释神经毒性。生长神经元顶端的生长锥体已被证明对局麻药的神经毒性不稳定。几种神经营养因子促进暴露在局部麻醉剂下的神经元的恢复。在本研究中，我们证明了甲比卡因、布比卡因和罗比卡因具有与生长锥体和生长轴突相似的神经毒性，神经营养因子NT-3、BDNF、GDNF在局部麻醉剂损伤后具有促进神经元存活和再生的潜力。丁卡因作用后，细胞内钙离子从生长轴突的顶端开始升高。抬高的方式不是尖峰，而是缓慢抬高，意味着膜完整性的损害。

Local anesthetics impair morphology of neurons and disturb physiological nerve conduction. Especially, lidocaine and tetracaine are most toxic among the commercially available local anesthetics. Apoptosis is one of the basic mechanism of the neurotoxity, however, recent publications described that the toxicity could not be thoroughly explained by apoptosis. Growth cones at the tip of growing neurons have been demonstrated as labile to the neurotoxicity of local anesthetics. Several neurotrophic factors promote the recovery of neurons that are exposed to local anesthetics. In the present study, we have demonstrated that mepivacaine, bupivacaine and ropivacaine have similar neurotoxity to growth cones and growing neurites, and that neurotrophic factors, NT-3, BDNF, GDNF, have potential to promote neuronal survival and regeneration following the injury by local anesthetics. Intracellular calcium ion elevation was observed after the exposure to tetracaine beginning from the tip of growing neurite. The way of elevation was not spiky but slowly elevating, and implied impairment of membrane integrity.