碱性成纤维细胞生长因子诱导大鼠受损视神经胶质细胞去分化

bFGF induced dedifferentiation of glial cells in injured rat optic nerve

目的研究碱性成纤维细胞生长因子(bFGF)促进大鼠受损视神经修复及诱导胶质细胞去分化的机制。方法成年SD大鼠55只随机分为正常对照组、损伤组、bFGF组。术后7d取眶内段视神经行Agilent基因芯片、实时荧光定量PCR检测;术后7d、14d取眶内段视神经行HE、免疫组织化学等检测。结果术后7d,bFGF组与损伤组相比有645条基因上调,458条下调,其中包括与神经干细胞或前体细胞及神经发育、增殖凋亡、染色质构型、转录调节、信号转导、神经生长相关基因等。与损伤组相比,bFGF组受损视神经远侧段细胞核增大,细胞数量增加,巢蛋白、细胞外信号调节激酶1/2(ERK1/2)、胶质纤维酸性蛋白(GFAP)、髓鞘碱性蛋白(MBP)阳性物质增加,近侧段神经丝(NF)阳性物质增加。结论外加bFGF能促进受损视神经细胞增殖,增强神经胶质细胞去分化变化,同时改善神经再生的抑制性微环境,促进视神经再生。

Objective To investigate the mechanism that bFGF promotes the regeneration of injured optic nerve and induces dedifferentiation of glial ceils in it. Methods Fifty-five adult male SD rats were randomly divided into 3 groups as normal control group, injury group and bFGF group. At day 7 post operation, optic nerves from injury group and bFGF group were detected by gene chip and real-time PCR. At day 7, 14 post operation, optic nerves were harvested and detected by HE staining and immunohistochemistry. Results Compared with the injury group, there were 645 genes expression up-regulated and 458 genes down-regulated including genes related neural stem cell or precursor cell neural development, proliferation, apoptosis, cbromatin configuration, transcription regulation, signal transduction, neural growth and so on in the bFGF group. There were bigger nuclei, more cells, more immunoreactivity of nestin, extracellular signalregulated kinase（Erk1/2）, glial fibrillary acidic protein （GFAP） , and myelin basic protein （MBP） in the distal optic nerves and more immunoreactivity of neurofilament（NF） in the proximal optic nerves in the bFGF group than that in the injury group. Conclusion bFGF could promote the proliferation of neuroglia cells, dedifferentiation of neural glias and improve the microenvironment to favour the regeneration of injured optic nerve.