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Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage

机译:bis(7)-他克林对谷氨酸诱导的视网膜神经节细胞损伤的神经保护作用

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Background Glutamate-mediated excitotoxicity, primarily through N-methyl-D-aspartate (NMDA) receptors, may be an important cause of retinal ganglion cells (RGCs) death in glaucoma and several other retinal diseases. Bis(7)-tacrine is a noncompetitive NMDA receptors antagonist that can prevent glutamate-induced hippocampal neurons damage. We tested the effects of bis(7)-tacrine against glutamate-induced rat RGCs damage in vitro and in vivo. Results In cultured neonatal rats RGCs, the MTT assay showed that glutamate induced a concentration- and time-dependent toxicity. Bis(7)-tacrine and memantine prevented glutamate-induced cell death in a concentration-dependent manner with IC50 values of 0.028 μM and 0.834 μM, respectively. The anti-apoptosis effects of bis(7)-tacrine were confirmed by annexin V-FITC/PI staining. In vivo, TUNEL analysis and retrograde labeling analysis found that pretreatment with bis(7)-tacrine(0.2 mg/kg) induced a significant neuroprotective effect against glutamate-induced RGCs damage. Conclusions Our results showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced RGCs damage in vitro and in vivo, possibly through the drug's anti-NMDA receptor effects. These findings make bis(7)-tacrine potentially useful for treating a variety of ischemic or traumatic retinopathies inclusive of glaucoma.
机译:背景谷氨酸介导的兴奋性毒性可能主要通过N-甲基-D-天冬氨酸(NMDA)受体引起,可能是青光眼和其他几种视网膜疾病中视网膜神经节细胞(RGC)死亡的重要原因。 Bis(7)-他克林是一种非竞争性NMDA受体拮抗剂,可以预防谷氨酸诱导的海马神经元损伤。我们在体外和体内测试了bis(7)-他克林对谷氨酸诱导的大鼠RGC损伤的作用。结果在培养的新生大鼠RGC中,MTT分析表明谷氨酸诱导了浓度和时间依赖性的毒性。 Bis(7)-他克林和美金刚胺以浓度依赖的方式阻止了谷氨酸诱导的细胞死亡,IC50值分别为0.028μM和0.834μM。膜联蛋白V-FITC / PI染色证实了bis(7)-他克林的抗凋亡作用。在体内,TUNEL分析和逆行标记分析发现,用bis(7)-他克林(0.2 mg / kg)进行预处理可对谷氨酸诱导的RGC损伤产生明显的神经保护作用。结论我们的结果表明,bis(7)-他克林对谷氨酸诱导的RGC损伤具有神经保护作用,可能是通过药物的抗NMDA受体作用引起的。这些发现使bis(7)-他克林潜在地可用于治疗包括青光眼在内的多种缺血性或外伤性视网膜病。

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