大鼠受损视神经去分化相关基因表达谱的变化及移植预变性腓总神经的作用

Changes of gene expression profile associated with dedifferentiation and effect of predegenerated peroneal nerve in injured optic nerve of rat

为检测受损视神经基因表达谱的变化以及移植预变性周围神经的调节作用,SD大鼠随机分为正常组、损伤组和神经移植组,术后7 d取眶内段视神经,用Aglient Oligo芯片检测其基因表达谱的变化,并用实时荧光定量PCR、免疫组织化学、Western Blot验证芯片检测结果。损伤组与正常组相比,1340条基因上调,940条基因下调;去分化相关基因如神经发育早期基因表达上调,转录、凋亡、增殖、生长、分化和细胞内信号转导类差异表达基因较多,基因差异表达的变化以有利于神经再生为主,但也存在显著抑制神经再生的差异表达变化。神经移植组与损伤组相比,106条基因上调,14条基因下调,部分差异表达基因与细胞去分化有关。总之,视神经损伤早期约1/10的基因差异表达,其中包含与神经胶质细胞去分化密切相关的基因;移植预变性周围神经可调控受损视神经中部分基因的表达,促使胶质细胞去分化趋势增强,有利于视神经再生。

The aim of this study is to find out changes of gene expression profile in injured optic nerves and the effect of autograft predegenerated nerves on it. SD rats were randomly divided into normal group, injury group and nerve transplantation group. On day 7 post operation, intraorbital optic nerves were harvested for detecting the changes of gene expression profile with Agilent Oligo chips. After that, the gene expression profile was confirmed with real-time quantitative PCR, immunohistochemistry and Western Blot. Compared with the normal group, 1 340 genes were up-regulated and 940 genes were down-regulated in the injury group. Some genes associated with dedifferentiation, such as genes expressing in the early stage of nerve development, were up-regnlated. There were notably differential expressions for some genes related to transcription, apoptosis, proliferation, growth, differentiation or intracellular signal transduction, gene expression changes mostly benefit optic nerve regeneration; but some changes were remarkably related to inhibition of nerve regeneration. Compared with the injury group, 106 genes were up-regulated, and 14 genes were down-regulated in the nerve transplantation group, some of which were related to cell dedifferentiation. After optic nerve injury, about 1/10 genes were differentially expressed, some of which might be related to dedifferentiation. Predegenerated peripheral nerves could partially regulate the gene expressions in the injured optic nerves, and stimulate the dedifferentiation of glial cells which finally promote optic nerve regeneration.