Yang Jin-nan, Zhan He-qin, Chen Jin-mao, Lin Shao-chun, Li Dai, Hu Shi-xing
College of Pharmacy, Xinxiang Medical College, Xinxiang 453003, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2006 May;26(5):603-5.
To observe the changes of nuclear factor-kappa B (NF-kappaB) 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.
A single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats, which were sacrificed at different intervals after 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-kappaB.
Pyknosis of the photoreceptor cell nuclei and disorientation of the outer segment of the photoreceptor layer was observed 24 h after 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-kappaB p65 protein was only detected 12 and 24 h after MNU treatment, whereas the amount of I kappa B alpha, in contrast, markedly increased in the cytoplasm as well as in the nuclei.
MNU-induced retinal damage might be mediated through the signaling pathway of NF-kappaB/I kappa B alpha.
观察核因子-κB（NF-κB）在N-甲基-N-亚硝基脲（MNU）诱导大鼠视网膜光感受器细胞凋亡过程中的变化，探讨MNU致视网膜损伤的机制。
对50日龄雌性大鼠单次腹腔注射60mg/kg MNU，于MNU处理后不同时间点处死大鼠。用光学显微镜检查视网膜损伤情况，采用TUNEL法检测光感受器细胞凋亡。进行蛋白质免疫印迹法分析NF-κB的变化。
MNU处理24小时后可见光感受器细胞核固缩，光感受器层外节排列紊乱，第7天时外核层和光感受器层几乎完全消失。光感受器细胞凋亡在24小时达到高峰，在凋亡级联反应中，仅在MNU处理12小时和24小时后检测到NF-κB p65蛋白，而与之相反，IκBα在细胞质和细胞核中的含量均显著增加。
MNU诱导的视网膜损伤可能通过NF-κB/IκBα信号通路介导。
