Binda Nancy Scardua, Carayon Charles Porto Petruceli, Agostini Rafael Mourão, Pinheiro Ana Cristina do Nascimento, Cordeiro Marta Nascimento, Silva Marco Aurélio Romano, Silva Juliana Figueira, Pereira Elizete Maria Rita, da Silva Junior Claudio Antonio, de Castro Junior Célio José, Guimarães Andre Luiz Sena, Gomez Marcus Vinicius
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil.
Ezequiel Dias Foundation (FUNED), Laboratory of Biochemistry, Rua Conde Pereira Carneiro 80, Belo Horizonte, Minas Gerais 30510-010, Brazil.
Toxins (Basel). 2016 Mar 11;8(3):70. doi: 10.3390/toxins8030070.
The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-D-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels.
蜘蛛毒素N-P/Q钙通道阻滞剂PhTx3-4在N-甲基-D-天冬氨酸（NMDA）诱导的大鼠视网膜损伤模型中的体内神经保护作用进行了研究。NMDA诱导的大鼠视网膜损伤使b波振幅降低了62%±3.6%，表明损伤的严重程度。PhTx3-4治疗增加了b波的振幅，这几乎与未受损伤的对照视网膜相当。在视网膜细胞的神经保护中也观察到了PhTx3-4对视网膜的功能保护作用，这在视网膜电图上有所记录。NMDA诱导的损伤减少了视网膜各层的活细胞，其中神经节细胞层减少最多，达84%。值得注意的是，PhTx3-4治疗使视网膜各层的死细胞显著减少，其中对神经节细胞层的神经保护作用最为明显。NMDA诱导的视网膜细胞毒性增加了谷氨酸的释放、活性氧（ROS）的产生和氧化应激。PhTx3-4治疗减少了谷氨酸的释放、ROS的产生以及通过丙二醛测量的氧化应激。因此，我们首次提出证据表明，蜘蛛毒素PhTx3-4（-ctenitoxin-Pn3a）可阻断N-P/Q钙通道，对NMDA诱导的视网膜损伤具有体内神经保护作用。
