N-methyl-N-nitrosourea induces retinal degeneration in the rat via the inhibition of NF-B activation
N-methyl-N-nitrosourea induces retinal degeneration in the rat via the inhibition of NF-B activation
复制标题
N-甲基-N-亚硝基脲通过抑制 NF-B 激活诱导大鼠视网膜变性
DOI：
10.1002/cbf.3232
复制
发表时间：
2016
影响因子：
3.6
通讯作者：
Xia Xiao-bo
中科院分区：
文献类型：
--
作者：
Xiong Yu;Ji Hong-pei;Song Wei-tao;Yin Ye-Wei;Xia Chao-hua;Xu Bei;Xu Yi;Xia Xiao-bo
视网膜色素变性（RetinitisPigmentosa，RP）是一组遗传性神经退行性疾病，其特征是感光细胞通过凋亡而丧失。N-甲基-N-亚硝基脲（MNU）是一种烷化剂，可诱导感光细胞死亡，类似遗传性RP。本研究旨在探讨核因子κB（NF-κB）在MNU诱导的光感受器变性中的作用。成年大鼠接受单次腹腔注射MNU（60 mg/kg体重）。苏木精-伊红染色显示MNU处理后外核层（ONL）逐渐丢失。透射电子显微镜检查显示核固缩、光感受器染色质边缘化、次级溶酶体增加以及分叶状视网膜色素上皮cells.in MNU处理的大鼠。ONL中大量的感光细胞TUNEL染色阳性，凋亡率在24小时达到高峰。增强深度成像光谱域光学相干断层扫描显示ONL变薄和脉络膜厚度减少。视网膜电图显示A波振幅下降，在暗视条件下占优势。Western blot分析显示，MNU处理组大鼠视网膜核IκBα水平升高，而核NF-κB p65水平显著降低。这些发现表明MNU导致选择性光感受器降解，并且这与抑制NF-κB活化有关。
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by the loss of photoreceptor cells through apoptosis. N‐methyl‐N‐nitrosourea (MNU) is an alkylating toxicant that induces photoreceptor cell death resembling hereditary RP. This study aimed to investigate the role of nuclear factor κB (NF‐κB) in MNU‐induced photoreceptor degeneration. Adult rats received a single intraperitoneal injection of MNU (60 mg/kg bodyweight). Hematoxylin and eosin staining demonstrated progressive outer nuclear layer (ONL) loss after MNU treatment. Transmission electron microscopy revealed nuclear pyknosis, chromatin margination in the.photoreceptors, increased secondary lysosomes, and lobulated retinal‐pigmented epithelial cells.in MNU‐treated rats. Numerous photoreceptor cells in the ONL showed positive TUNEL staining.and apoptosis rate peaked at 24 hours. Enhanced depth imaging spectral‐domain optical coherence tomography showed ONL thinning and decreased choroid thickness. Electroretinograms.showed decreased A wave amplitude that predominated in scotopic conditions. Western blot.analysis showed that nuclear IκBαlevel increased, whereas nuclear NF‐κB p65 decreased significantly in the retinas of MNU‐treated rats. These findings indicate that MNU leads to selective.photoreceptor degradation, and this is associated with the inhibition of NF‐κB activation.