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利多卡因和阿替卡因对神经元存活及恢复的影响。

Effects of Lidocaine and Articaine on Neuronal Survival and Recovery.

作者信息

Albalawi Farraj, Lim Jason C, DiRenzo Kyle V, Hersh Elliot V, Mitchell Claire H

机构信息

Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania.

Department of Orthodontics, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania.

出版信息

Anesth Prog. 2018 Summer;65(2):82-88. doi: 10.2344/anpr-65-02-02.

Abstract

The local anesthetics lidocaine and articaine are among the most widely used drugs in the dentist's arsenal, relieving pain by blocking voltage-dependent Na channels and thus preventing transmission of the pain signal. Given reports of infrequent but prolonged paresthesias with 4% articaine, we compared its neurotoxicity and functional impairment by screening cultured neural SH-SY5Y cells with formulations used in patients (2% lidocaine + 1:100,000 epinephrine or 4% articaine + 1:100,000 epinephrine) and with pure formulations of the drugs. Voltage-dependent sodium channels Na(v)1.2 and Na(v)1.7 were expressed in SH-SY5Y cells. To test the effects on viability, cells were exposed to drugs for 5 minutes, and after washing, cells were treated with the ratiometric Live/Dead assay. Articaine had no effect on the survival of SH-SY5Y cells, while lidocaine produced a significant reduction only when used as pure powder. To determine reversibility of blockage, wells were exposed to drugs for 5 minutes and returned for medium for 30 minutes, and the calcium elevation induced by depolarizing cells with a high-potassium solution was measured using the calcium indicator Fura-2. High potassium raised calcium in control SH-SY5Y cells and those treated with articaine, but lidocaine treatment significantly reduced the response. In conclusion, articaine does not damage neural cells more than lidocaine in this in vitro model. While this does not question the safety of lidocaine used clinically, it does suggest that articaine is no more neurotoxic, at least in the in vitro setting.

摘要

局部麻醉药利多卡因和阿替卡因是牙医常用药物中使用最广泛的药物之一,它们通过阻断电压依赖性钠通道来缓解疼痛,从而阻止疼痛信号的传递。鉴于有报道称4%阿替卡因会导致罕见但持续时间较长的感觉异常,我们通过用患者使用的配方(2%利多卡因+1:100,000肾上腺素或4%阿替卡因+1:100,000肾上腺素)以及药物的纯配方筛选培养的神经SH-SY5Y细胞,比较了其神经毒性和功能损害。电压依赖性钠通道Na(v)1.2和Na(v)1.7在SH-SY5Y细胞中表达。为了测试对细胞活力的影响,将细胞暴露于药物中5分钟,洗涤后,用比例活/死检测法处理细胞。阿替卡因对SH-SY5Y细胞的存活没有影响,而利多卡因仅在用作纯粉末时才会导致显著降低。为了确定阻断的可逆性,将孔暴露于药物中5分钟,然后更换为培养基30分钟,并使用钙指示剂Fura-2测量用高钾溶液使细胞去极化诱导的钙升高。高钾可使对照SH-SY5Y细胞和用阿替卡因处理的细胞中的钙升高,但利多卡因处理显著降低了反应。总之,在这个体外模型中,阿替卡因对神经细胞的损伤并不比利多卡因更大。虽然这并不质疑临床使用利多卡因的安全性,但这确实表明阿替卡因至少在体外环境中神经毒性并不更强。

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