N-甲基-N-亚硝脲诱导的大鼠视网膜感光细胞损伤模型中Müller细胞增殖和细胞因子分泌的变化  

Changes of Miiller cell proliferation and growth factor secretion of rat retina with photoreceptor degeneration induced by N-methyl-N-nitrosourea

作　　者：王芳[1] 万瑾[1] 肖虹蕾[1] 余振珏[1] 周国民[1] 

机构地区：[1]复旦大学上海医学院解剖与组织胚胎学系,上海200032

出　　处：《解剖学杂志》2007年第2期171-173,214,F0002,共5页Chinese Journal of Anatomy

基　　金：国家重点基础研究发展规划"973"攻关项目(2005CB724300-G);国家自然科学基金(30270699)

摘　　要：目的:建立N-甲基-N-亚硝脲(N-methyl-N nitrosourea,MNU)损伤视网膜的模型,研究视网膜神经元凋亡对Müller细胞生物学特性的影响及神经营养因子的表达变化。方法:腹腔注射MNU建立视网膜损伤模型,免疫荧光染色方法研究感光细胞缺失对Müller细胞的生物学特性的影响,并检测主要神经营养因子表达的变化。结果:TUNEL法显示,腹腔注射MNU后2 d,视网膜外核层细胞凋亡现象明显。核增殖抗原(PCNA)及细胞周期素CyclinD_1的表达明显增高。与此同时,Müller细胞也开始表达神经干细胞抗原巢蛋白(nestin);RT-PCR显示胰岛素样生长因子(IGF),碱性成纤维细胞生长因子(bFGF)和肝细胞生长因子(HGF)mRNA的表达均升高。结论:在视网膜受到损伤时,Müller细胞增殖、去分化呈现出干细胞的特性。而视网膜中IGF、bFGF和HGF等细胞因子的表达明显增高,提示视网膜损伤后可能通过大量分泌细胞生长因子,促进Müller细胞的增殖。Objective： To establish the model of retinal injury induced by N-methyl-N-nitrosourea （MNU） in Sprague- Dawley rats, then observe the apoptosis of the photoreceptors and the change of the biological characteristics of Müller cells. Methods： Sprague-Dawley rats were injected with MNU （60 mg/kg） intraperitoneally, and the apoptosis of the photoreceptors and the expression of insulin-like growth factor （IGF）, basic fibroblast growth factor （bFGF）, hepatocyte growth factor （HGF） and CyclinD1 mRNA were detected by TUNEL assay and RT-PCR. Results： Two days after MNU treatment, the apoptotic cells were obvious in the outer nuclear layer. By immunohistochemistry, we found that proliferating cell nuclear atigen （PCNA） and nestin were stained positive in the inner nuclear layer （INL） and co-localized with GS. The expression of IGF, bFGF and HGF mP, NA in the test group began to increase after MNU treatment. Conclusion： Müller cells proliferate and dedifferentiate when neurons in the retina, such as the photoreceptor cells, give rise to apoptosis. The increased expressions of IGF, bFGF and HGF mRNA after MNU treatment in the retina suggest that retina injury can increase the secretion of growth factor to promote the proliferation of Müller cells.

关 键 词：N-甲基-N-亚硝脲 MÜLLER细胞 成纤维细胞生长因子 肝细胞生长因子 胰岛素样生长因子 

分 类 号：R774.1[医药卫生—眼科]