Lidocaine toxicity to rat retinal ganglion cells.
Lidocaine toxicity to rat retinal ganglion cells.
复制标题
利多卡因对大鼠视网膜神经节细胞的毒性。
DOI：
10.1076/ceyr.18.5.363.5349
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发表时间：
1999
影响因子：
2
通讯作者：
Dreyer,EB
中科院分区：
文献类型：
--
作者：
Grosskreutz,CL;Katowitz,WR;Freeman,EE;Dreyer,EB
目的观察局麻药利多卡因对大鼠视网膜神经节细胞（RGC）的体外及改良的体内影响。方法体外实验采用龙眼大鼠幼鼠视网膜分离制备RGC。RGC与不同浓度的利多卡因（0.5-12.0 mM）孵育过夜。24小时检测存活细胞。在体内实验中，将7日龄的龙-埃文斯大鼠幼仔麻醉后，玻璃体内注射2µl利多卡因（眼内终浓度：0.03-15 mM）或对照物。还对一部分动物进行了尼莫地平或MK801（地佐西平）玻璃体腔内联合注射。注射后1周，处死大鼠幼鼠，摘除视网膜，分离，分别镀膜。立即评估RGC生存期。活研资局以形态学为基础进行识别，并以蒙面方式进行计数。结果利多卡因对RGC体外毒性呈剂量依赖性。较低浓度（0.5 mM和1.0 mM）无毒；2.0 mM、6.0 mM和12.0 mM利多卡因分别杀死了25%、88%和99%的RGC。玻璃体内注射利多卡因对RGC也有剂量依赖性毒性。利多卡因浓度为3.0 mM、7.5 mM和15 mM时，RGC的死亡率分别为25%、38%和44%。同时给予尼莫地平或MK801可阻断该效应。结论利多卡因对RGC有体外和体内毒性。这种作用在体内被同时服用已知的阻断谷氨酸介导的神经元死亡的药物所阻断，这表明兴奋性毒性可能参与了这一过程。
PurposeTo examine the effects of the local anesthetic, lidocaine, on rat retinal ganglion cells (RGC) in vitro and in a modified in vivo assay.MethodsFor in vitro experiments, RGC were dissociated from freshly harvested Long Evan's rat pup retinas. The RGC were incubated overnight with varying concentrations of lidocaine (0.5–12.0 mM). Surviving cells were assayed at 24 hours. In an in vivo assay, 7-day-old Long-Evans rat pups were anesthetized and 2 µl of lidocaine (final intraocular concentration: 0.03–15 mM) or vehicle was injected intravitreally. Intravitreal coinjection of nimodipine or MK801 (dizocilpine) were also performed in a subset of animals. A week after injection, rat pups were sacrificed and each retina removed, dissociated and plated separately. RGC survival was immediately assessed. Living RGC were identified on the basis of morphology and counted in a masked fashion.ResultsLidocaine is toxic in a dose dependent fashion to RGC in vitro. Lower concentrations (0.5 mM and 1.0 mM) were non-toxic; 2.0, 6.0 and 12.0 mM lidocaine killed 25%, 88% and 99% of the RGC respectively. Intravitreal lidocaine was also toxic to RGC in a dose dependent fashion. Lidocaine concentrations of 3.0 mM, 7.5 mM and 15 mM killed 25%, 38% and 44% of the RGC. This effect was blocked by the simultaneous administration of either nimodipine or MK801.ConclusionsLidocaine is toxic to RGC both in vitro and in vivo. This effect is blocked in vivo by the simultaneous administration of agents known to block glutamate mediated neuronal death, suggesting that excitotoxicity may be involved in this process.