碱性成纤维细胞生长因子转基因治疗对放射性脑损伤大鼠星形胶质细胞相关蛋白表达的影响

Effect of bFGF gene transfection on expression of astrocytes associated protein in rats with radiation induced brain impairment

目的观察碱性成纤维细胞生长因子（bFGF）转基因治疗对全脑放射后脑损伤（radiation in—juries of brain，RIB）模型鼠星形胶质细胞胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）和波形蛋白（Vimentin，VIM）表达的影响，为探索治疗RIB的新途径提供实验基础。方法分组采用直线加速器对Sprague-Dawley大鼠进行全脑单次25Gy照射建立RIB模型，bFGF转基因治疗组采用侧脑室注射bFGF-pcDNA3．1（＋）质粒，并设未照射组为对照。在照射前及照射后20d和60d分别观察各组脑组织GFAP和VIM表达情况。结果照射组病理检查显示海马和皮层神经元轻度变性，胞体萎缩，白质区域较对照组呈现组织结构梳松、血管周隙扩大等表现；bFGF治疗组病变程度明显较照射组轻。各组大鼠照射后GFAP表达均增加，20d时bFGF治疗组GFAP阳性细胞数[（65±6．2）个]高于照射组[（49±5．8）个]和对照组[（184±2．4）个]（P〈0．05），60d时bFGF治疗组GFAP阳性细胞数（44±5．1）较20d时明显减少（P〈0．05），其他各组GFAP阳性细胞数与20d时无显著性差别（P〉0．05）。bFGF治疗组照射后20dVIM表达（0．944±0．12）较照射组（1．45±0．26）明显减少（P〈0．05），60d时各组VIM表达量无显著性差别。结论25Gy射线照射可提高RIB鼠脑GFAP和VIM急性期表达量，bFGF转基因治疗可增加急性期GFAP的表达，降低VIM表达。

Objective To observe the effect of basic fibroblast growth factor （bFGF） gene therapy on as- trocytes glial fibrillary acidic protein （glial fibrillary acidic protein, GFAP） and vimentin （Vimentin, VIM） protein expression of astroeytes in rats with whole brain radiation brain injury （RIB） in order to provide an experimental basis for exploring new ways to treat RIB. Methods Sprague-Dawley rats were grouped and received single 25Gy for whole brain irradiation to established brain radiation injury （ radiation injuries of the brain, RIB） model, bFGF gene therapy groups were given intracerebroventricular injection of bFGF-pcDNA3.1 （ ＋ ） plasmid and set non-ir-radiated group as control. Before irradiation and post-irradiation 20 d and 60 d, respectively, GFAP and VIM ex-pression were observed in each group of brain tissue. Results Radiation group with pathological examination showed mild degeneration of hippocampal and cortical neurons, and white matter regions presented the organization-al structure comb loose and perivascular space enlargement compared with the control group. But the bFGF treat-ment group was significantly lighter. The expression of GFAP were increased in each group after radiation. GFAP positive cells of bFGF treatment group （ 65 ± 6.2） were higher than that of irradiation group （49 ± 5.8 ） and con-trol group （ 18 ± 2.4） （P 〈 O. 05 ） at 20 d, GFAP positive cells at 60 d in bFGF treatment group （44 ± 5.1 ） were significantly reduced （P 〈 0. 05 ） than at 20 d and there were no significant difference （P 〉 0.05 ） in the other groups between 20 d and 60 d. VIM expression of bFGF treatment group was higher at 20 d （0.94 ±0.12） com-pared to irradiated group （ 1.45 ± 0.26） and no significant difference of VIM expression was found in each groups at 60 d. Conclusion Irradiation with 25Gy-ray can increase the expression of GFAP and VIM in rats brain at a-cute phase, bFGF gene therapy can increase the expression of GFAP and decrease the expression of VIM.