NADPH氧化酶在rd小鼠遗传性视网膜变性中的活化作用

Activation of NADPH Oxidase in the Retinal Degeneration in the Rd Mice

目的研究NADPH氧化酶在rd小鼠遗传性视网膜变性早期的活化表达及其氧化产物活性氧的生成,探讨其在遗传性视网膜变性早期的致病作用。方法以出生后8,10,12,14,16,18d的rd小鼠及对照鼠视网膜作为研究对象。Real-time PCR测定在rd小鼠感光细胞凋亡过程中视网膜NADPH氧化酶亚单位P22phox mRNA的定量表达。二氢乙锭(DHE)染色法测定NADPH氧化酶活化产物ROS的生成变化。结果与对照组相比,P22phox mRNA在rd小鼠出生后第12天表达明显升高,第14天达高峰。ROS在rd小鼠出生后第8天于视网膜外核层少量产生,第14天生成量达到高峰。结论在rd小鼠视网膜变性过程中NADPH氧化酶表达明显升高,ROS生成显著增加,皆早于或与感光细胞凋亡平行,提示NADPH氧化酶活化生成ROS可能在视网膜变性早期致病过程中发挥重要作用。

Objective To study the expression of NADPH oxidase and the production of ROS in the early rod degeneration in the rd mice and further explore its pathopoiesia in the retinitis pigmentosa .Methods Rd mice at postnatal day（P） 8,P10,P12,P14,P16 and P18 and their controls were studied .Expression levels of P22phox,a major subunit of NADPH oxidase ,was determined by real-time PCR.The production of ROS was detected by Dihydroethidium （DHE） staining.Results Compared with controls,the expression levels of transcripts of P22phox in the rd retinas star-ted to increase at P12 and peaked at P14.The production of ROS began to appear in the inner retina of rd mice at P 8d, peaking outer nuclear layer （ ONL） at P14d.Conclusion Expression of NADPH oxidase and production of ROS are up-regulated in the retinal degeneration in the rd mice and both before or paralleled to the photoreceptor degeneration ,sug-gesting that NADPH oxidase and ROS may play a role in the early retinal degeneration .