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学习记忆能力的改善作用  

The therapic effect of bFGF gene transfection on radiation induced learning and memory impairment of rats

作　　者：刘运林[1] 周海红[2] 刘军[3] 肖颂华[3] 邢诒刚[3] 

机构地区：[1]山东省泰安市中心医院,泰安271000 [2]广东医学院附属医院神经内科 [3]中山大学附属第二医院神经内科

出　　处：《中华行为医学与脑科学杂志》2009年第9期781-783,共3页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：基金项目：国家自然科学基金资助项目（30870750）;泰安市科技发展计划项目（20083023）

摘　　要：目的观察碱性成纤维细胞生长因子（basic fibroblast growth factor，bFGF）转基因治疗对放射性脑损伤（RIB）模型鼠学习记忆能力的影响，为探索治疗RIB的新途径提供实验基础。方法PCR法克隆出bFGF基因片段，酶切后连接法构建bFGF．pcDNA3．1（＋）质粒。分组采用直线加速器对Sprague—Daw—ley大鼠进行全脑单次25Gy照射，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7d，20d，60d分别进行Morris水迷宫试验，分析各组大鼠行为学检测结果，采用平均逃避潜伏期和搜索策略2个指标评价大鼠学习记忆能力，同时观察各组脑组织病理变化。结果各组大鼠放射前平均逃避潜伏期和搜索策略得分无统计学差异，bFGF治疗组、照射组和对照组在照射后不同时间点平均潜伏期和搜索策略差异有显著性（P〈0．05））。bFGF治疗组在放射后7d、20d平均逃避潜伏期[（68．42±11．35）s、（50．87±12．06）s]和搜索策略[（16．89±2．08）％、（19．98±2．14）％1明显下降，60d时潜伏期[（40．28±10．87）S]和搜索策略[（26．42±2．59）％]恢复至照射前水平，放射组60d后仍没有恢复。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。结论25Gy射线照射可降低大鼠学习记忆能力，bFGF转基因治疗可逆转放射造成的大鼠学习记忆能力下降。Objective To study the effects of basic fibroblast growth factor（bFGF） transfection therapy on learning and memory ability of radiation brain injuries rat model. Methods The bFGF gene was cloned by PCR method and linked to pe-DNA3.1 （ ＋ ） plasmid. Sprague-Dawley rats were grouped to 3 groups and received different treatment. The rats of bFGF group were injected bFGF-pcDNA3.1 （ ＋ ） plasmid into lateral ventricle after radiation and the rats of radiation group were only received single 25 Gy radiation by linear accelerator. Control group was set for contrast. Before radiation and 7,20,60 days after radiation, Morris maze test were taken to study the learning and memory ability of rats in each group. Average escape latency（AEL） and search strategy（SS） were scaled and analyzed. Pathology examinations were taken in every group. Results No statistic differences of AEL and SS were found in each group before radiation. After radiation,learning and memory ability of rats in each group were dramatically changed（ P 〈 0.05 ）. The scales of ALE in bFGF group were decreased after 7 and 20 days [（68.42±11.35）s,（50.87 ± 12.06）s3 and so were the scales of SS [（16.89 ±2.08）%,（19.98 ± 2.14 ） % ] and recovered after 60 days [ AEL ： （ 40.28 ：t 10.87 ） s ; SS ： （ 26.42 ± 2.59 ） % ] but no recoveries were found in radiation and control group after 60 days of radiation. Neurons were atrophic degenerated and whiter mat- ter were loosen in radiation group but the pathologic changes were lessen in bFGF groups. Conclusion The im- pairment of learning and memory ability caused by 25Gy radiation can be reversed by bFGF transgenic therapy.

关 键 词：放射性脑损伤 学习记忆 转基因治疗 碱性成纤维细胞生长因子 大鼠 

分 类 号：R285.5[医药卫生—中药学]