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作 者:杨锦南[1] 詹合琴[1] 陈金卯[2] 林少春[2] 李岱[2] 胡世兴[2]
机构地区:[1]新乡医学院药学院,河南新乡453003 [2]中山大学中山眼科中心,广东广州510060
出 处:《南方医科大学学报》2006年第5期603-605,共3页Journal of Southern Medical University
基 金:国家自然科学基金(30300467)~~
摘 要:目的观察核因子κappaB(NF-κB)在N-甲基-N-亚硝脲(MNU)诱导大鼠视网膜光感受器细胞凋亡中的的变化,探讨MNU损伤视网膜的机制。方法给生后50d的雌性SD大鼠一次腹腔注射MNU60mg/kg,分别在MNU处理不同时间后处死动物。光学显微镜观察视网膜的形态学变化;TUNEL试剂盒检测光感受器细胞凋亡;Westernblotting分析NF-κB。结果MNU处理后24h,视网膜光感受器细胞核固缩和光感受器细胞层外节部定向障碍;7d后,外颗粒层和光感受层几乎完全消失。光感受器细胞凋亡在MNU处理后24h达高峰。在凋亡发生的过程中,仅在MNU作用12h和24h后,胞核内有低水平的p65蛋白。相反,胞浆和胞核内的κB蛋白水平呈时间依赖性地显著增加。结论NF-κB/IκBα信号通路的激活可能介导了MNU所致的视网膜损伤。Objective To observe the changes of nuclear factor-Kappa B (NF-KB) in the course of N-methyl-N-nitrosourea (MNU)-induced apoptosis of rat retinal photoreceptor cells and investigate the mechanism of MNU-induced retinal damage. Methods A single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats, which were sacrificed at different intervals aider MNU treatment. The retinal damage was examined with optical microscopy and photoreceptor cell apoptosis detected by TUNEL assay. Western blotting was performed to analyze the changes in NF-κB. Results Pyknosis of the photoreceptor cell nuclei and disorientation of the outer segment of the photoreceptor layer was observed 24 h aider MNU treatment, and the outer nuclear layer and photoreceptor layer were almost completely lost on day 7. Photoreceptor cell apoptosis peaked at 24 h, and in the apoptotic cascade, NF-κB p65 protein was only detected 12 and 24 h aider MNU treatment, whereas the amount of IκBα, in contrast, markedly increased in the cytoplasm as well as in the nuclei. Conclusion MNU-induced retinal damage might be mediated through the signaling pathway of NF-κB/IκBα.
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