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暗室环境可抑制氨己烯酸的视网膜毒性
Neuronal Plasticity Induced by Vigabatrin Can Be Suppressed by Darkness in the Mouse Retina
【摘要】 目的:观察新型抗癫癇药氨己烯酸的视网膜毒性与光毒性的关系,探索氨己烯酸视网膜损伤的预防机制。方法:选用30只健康雄性BALB/c小鼠。正常治疗组(n=10),置于正常饲养环境中(黑暗与光照交替12h),给予氨己烯酸250mg··-1腹腔注射;暗室治疗组(n=10),24h置于暗室环境中,药物治疗浓度同正常治疗组;对照组(n=10),置kg-1d于正常饲养环境中,给予0.9%NaCl0.1mL·-1,腹腔注射。1个月后处死小鼠取视网膜进行5种抗体(Anti-VGLUT、Anti-dBsaaoon、Anti-Goα、Anti-PKCα和Anti-calbindin)的免疫荧光染色。结果:5种抗体染色表明暗室治疗组小鼠的视杆细胞突触、ON-双极细胞突触、水平细胞突触由视网膜外丛状层(OPL)向外核层(ONL)的退缩在暗室环境中可被抑制。结论:氨己烯酸的小鼠视网膜毒性有光依赖性,去除光毒性的影响,小鼠视网膜第一与第二级神经元之间的病理性突触改变可被完全抑制。
【Abstract】 Aim: Todetect the correlationbetween phototoxicityandvigabation-elicited retinal damage, and explore the potential management of vigabatrin toxicity on retina. Methods: 30 BALB/c male mice were separated to three groups. Ten mice received vigabatrin daily intraperitoneal injection were kept in normal day-night cycle situation as vigabatrin treatment group; another ten mice were kept in darkness during the whole process of vigabatrin intraperitoneal injection as vigabatrin darkness group; the residual ten animals which accepted vehicle solution injection were also kept in normal day-night cycle situation as the control group. The whole period of experiment also last thirty days, vigabatrin concentration and dose of injection were the same among them. The animals were sacrificed after 30 days and the retinas were taken out. Their immunostaining reactions with the five kinds of antibodies were observed and the results were repeated. Results: ① In vigabatrin darkness group, withdrawal of photoreceptor terminal were completely suppressed. ② VGB-elicited sprouting of bipolar cell dendrites disappeared in dark situation. ③ The horizontal dendrites migrationwere alsoinhibitedin vigabatrin darkness group. Conclusion: Darkness couldeliminate the distinctive neuro-plasticity completely on albino mouse retina demonstrated vigabatrin-induced damage are correlated with phototoxicity. It indicated a potential way of prevention of vigabatrin injury in clinic.
- 【文献出处】 中国临床神经科学 ,Chinese Journal of Clinical Neurosciences , 编辑部邮箱 ,2009年05期
- 【分类号】R742.1
- 【下载频次】72