骨髓间充质干细胞(MSCs)对N-甲基-N-亚硝脲(MNU)诱导的C57BL小鼠视网膜变性的治疗作用  

Therapeutic effects of mesenchymal stem cells (MSCs) on N-methyl-N-nitrosourea (MNU )-induced retinitis pigmentosa in C57BL mice

作　　者：王宝英[1] 胡成虎 俞小瑞[1,3] 

机构地区：[1]西安交通大学医学部基础医学院生物化学与分子生物学系,陕西省西安市710061 [2]西安组织工程与再生医学研究所,陕西省西安市710032 [3]西安交通大学教育部环境与疾病相关重点实验室,陕西省西安市710061

出　　处：《眼科新进展》2017年第9期810-815,共6页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:81271013);教育部高等学校博士点专项科研基金资助(编号:20120201110051)~~

摘　　要：目的观察骨髓间充质干细胞(mesenchymal stem cells,MSCs)对N-甲基-N-亚硝脲(N-methyl-N-nitrosourea,MNU)诱导的C57BL小鼠视网膜色素变性(retinitis pigmentosa,RP)的治疗作用。方法应用不同剂量(30 mg·kg^(-1)、45 mg·kg^(-1)、60 mg·kg^(-1)、75 mg·kg^(-1)、90 mg·kg^(-1))的MNU腹腔注射给予C57BL小鼠和MNU作用不同时间(1 d、3 d、7 d)后,通过视网膜电图(electroretinogram,ERG)和HE染色检测小鼠视网膜的电生理功能和组织形态变化,优化建立稳定的RP动物模型的最佳条件;在此动物模型的基础上,经玻璃体内注射和尾静脉注射给予MSCs移植,并应用ERG和HE染色评估MSCs对MNU诱导的RP的治疗作用。结果与对照组相比,30 mg·kg^(-1)、45mg·kg^(-1)剂量的MNU可引起视网膜形态和功能的轻微损伤,而60 mg·kg^(-1)及其以上剂量的MNU可使视网膜ERG波幅明显降低(均为P<0.001),视网膜外核层(outer nuclear layer,ONL)厚度明显变薄(P<0.001),损伤严重;与对照组相比,60 mg·kg^(-1)的MNU作用后1 d和3 d,视网膜ERG波形开始降低,形态结构开始出现ONL厚度变薄的损伤,作用7 d时,ERG波形呈现熄灭型(均为P<0.001),ONL厚度明显变薄(P<0.001),内外核层融合,损伤严重。与MNU单独作用组相比,60 mg·kg^(-1)MNU作用1 d后给予MSCs移植,7 d后MSCs组内ONL厚度增加(P<0.001),视网膜ERG波形趋于恢复(均为P<0.001)。结论MSCs移植对MNU诱导的视网膜退行性变有一定的治疗作用。Objective To investigate the therapeutic effects of mesenchymal stem cells （MSCs） on N-methyl-N-nitrosourea （MNU）-induced retinal degeneration in C57BL mice. Methods Different doses of MNU （30 mg · kg^-1,45 mg · kg^-1 ,60 mg · kg^-1 ,75 mg · kg^-1 and 90 mg · kg^-1 ） were injected to C57BL mice for 7 days. Then electroretinogram （ERG） detection and HE staining were performed to examine retinal electrophysiological function and morphological changes on day l, day 3 and day 7 after MNU treatment, respectively. Then we could explore the optimum condition to establish stable animal model of retinitis pigmentosa. MSCs were transplanted to C57BL mice by intravitreal or tail intravenous injection. Then ERG detection and HE staining were per- formed to evaluate the effect of MSCs on retinitis pigmentosa induced by MNU. Re- suits When compared with control group,30 mg · kg^-1 and 45 mg · kg^-1 MNU could cause mild retinal damage in morphology and function in mice;while 60 mg · kg^-1 and above dose of MNU induced serious retinal damage, leading to decreased ERG ampli- tude of the retina （ all P 〈0. 001 ） and outer nuclear layer （ONL） thickness （ all P 〈 0. 001 ）. On day 1 and day 3 after single dose of 50 mg ~ kg-l MNU injection,ERG ampli- tude of the retina was decreased,and outer nuclear layer thickness became thin; while the retinal damage was serious badly in morphological structure on day 7, with the ERG amplitude extinguished （ all P 〈 0.001 ）, ONL thickness thin （ all P 〈 0.001 ） and internal and external nuclear layer fusion. When compared with MNU alone treatment group, fol- lowing injection of 50 mg · kg^-1 MNU for l day MSCs were transplanted to C57BL mice by intravitreal or tail intravenous injection, and the amplitude of ERG and retinal ONL thickness were increased on day 7 after MSCs transplantation （ all P 〈0.001 ）. Conelu- sion MSCs transplantation has a certain therapeutic effect on MNU-induced retinitis pigmentosa in C57BL mice.

关 键 词：骨髓间充质干细胞 N-甲基-N-亚硝脲 视网膜色素变性 小鼠 

分 类 号：R774[医药卫生—眼科]