摘要目的 探讨rd小鼠遗传性视网膜变性光感受器细胞变性凋亡中内质网应激反应蛋白的表达变化.方法 实验研究.取出生后8、10、12、14、24 d的rd小鼠和同年龄段的正常对照C3B小鼠.免疫印迹法检验视网膜中GRP78/BiP、半胱天冬酶-12酶原(procaspase-12)和活性caspase-12、p-PERK、p-eIF2a蛋白表达变化.免疫荧光染色共聚焦显微镜观测GRP78/BiP、caspase-12、p-PERK和p-eIF2a的表达部位及表达量的变化.用SPSS单因素方差分析对数据进行统计学分析,以P＜0.01为差异有统计学意义.结果 伴随rd小鼠遗传性视网膜变性过程免疫印迹结果显示GRP78/Bip、半胱天冬酶-12酶原和活性caspase-12、p-PERK、p-eIF2a蛋白的表达上调,与正常对照组之间的差异具有统计学意义(F=65.82,55.76,152.29,50.54,20.91;P＜0.05);免疫荧光染色结果显示GRP78/Bip、easpase-12、p-PERK和p-eIF2a主要表达于视网膜光感受器细胞的内节和光感受器细胞核中.结论 在rd小鼠遗传性视网膜变性光感受器细胞变性凋亡中,内质网应激反应蛋白的激活对于光感受器细胞的凋亡具有重要作用.应用内质网应激反应调节剂可能对此类疾病起到有效治疗作甩.

abstractsObjective To investigate the expression of endoplasmic reticulum (ER) stress proteins in photoreceptor apoptosis in rd mouse (Pde6bRd1/Rd1).Methods Photoreceptor apoptosis in rd mouse was detected by terminal dUTP transferase nick end labeling (TUNEL).The protein expression of ER stress sensors including glucose-regulated protein-78 (GRP78/BiP),easpase-12,phospho-eukaryotic initiation factor 2α (elF2α) and phospho-pancreatic ER kinase (PERK) was examined by immunoflurescence and Western Blot analysis.Results Accompanying photoreceptor apoptosis in rd mouse,protein expression of GRP78/BiP,caspase-12,phospho-eIF2α and phospho-PERK was up-regulated in a time dependent manner.The up-regulation of these proteins coincided with or preceded the photoreceptor apoptosis.At the peak of their expression,they were mainly located in the photoreceptor inner segment and/or outer nuclear layer (ONL).Condusion Activation of ER stress proteins appears to play an important role in rd retinal degeneration.Therefore endoplasmic reticulum stress modulators could be a strong candidate as a therapeutic agent in the treatment of these diseases.