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

麻醉相关药物对神经元凋亡的影响：细胞内钙升高引起的酶活性改变。

• 批准号: 13671562
• 负责人: SAITO Sigeru
• 金额: $ 1.54万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671562/
• 关键词: local anesthetics; nerve growth cone; growth cone collapse; neurotoxicity; neurotrophic factor; intracellular calcium concentration; 細胞内カルシウム; テトラカイン; アポトーシス

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.

局麻药损害神经元的形态，干扰生理性神经传导。尤其是利多卡因和丁卡因在市售的局部麻醉剂中毒性最大。细胞凋亡是神经毒性的基本机制之一，但近年来的研究表明，细胞凋亡不能完全解释神经毒性。生长神经元顶端的生长锥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于局部麻醉剂的神经元的恢复。在本研究中，我们已经证明甲哌卡因、布比卡因和罗哌卡因对生长锥和生长的神经突起具有相似的神经毒性，并且神经营养因子NT-3、BDNF、GDNF具有促进局麻药损伤后神经元存活和再生的潜力。丁卡因暴露后，细胞内钙离子的升高，观察从尖端生长的神经突开始。其上升方式不是尖状的，而是缓慢上升的，这意味着膜完整性的损害。

项目成果

Radwan IA, Saito S, Goto F.: "The neurotoxicity of local anesthetics on growing neurons : a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine."Anesth Analg.. 94巻2号. 319-324 (2002)

Radwan IA、Saito S、Goto F.：“局部麻醉剂对生长神经元的神经毒性：利多卡因、布比卡因、甲哌卡因和罗哌卡因的比较研究。”Anesth Analg 94，第 2 期 319-324（2002 年）。

Nara T., Saito S., 他: "A Rat Model of Postthracotomy pain : Behavicural and Spinal Cord NK-1 Receptor Assessment"Canadian Journal of Anaesthesiology. 48・7. 665-676 (2001)

Nara T.、Saito S. 等：“大鼠胸膜切开术后疼痛模型：行为和脊髓 NK-1 受体评估”加拿大麻醉学杂志 48・7 (2001)。

Radwan I., Saito S., 他: "High Concentration Tetracaine for the Management of Trigeminal Neuralgia : Quantitative Assessment of Sensory Function After Peripheral Nerve Block"The Clinical Journal of Pain. 17・4. 323-326 (2001)

Radwan I.、Saito S.等人：“高浓度丁卡因治疗三叉神经痛：周围神经阻滞后感觉功能的定量评估”《临床疼痛杂志》17・4（2001）。

Radwan IA, Saito S, Goto F.: "Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors."Anesthesiology. 97-3. 630-635 (2002)

Radwan IA、Saito S、Goto F.：“利多卡因对 DRG 神经元的生长锥塌陷作用可被几种神经营养因子部分逆转。”麻醉学。

Saito S, Radwan I, Obata H, Takahashi K, Goto F.: "Direct neurotoxicity of tetracaine on growth cones and neurites of growing neurons in vitro."Anesthesiology. 95-3. 726-733 (2001)

Saito S、Radwan I、Obata H、Takahashi K、Goto F.：“丁卡因对体外生长神经元的生长锥和神经突的直接神经毒性。”麻醉学。