BDNF基因修饰骨髓间充质干细胞对AD大鼠认知障碍的改善

Improvement of learning and memory impairment of Alzheimer's disease rat models treated by bone mesenchymal stem cells modified with BDNF gene

目的:研究经侧脑室移植脑源性神经生长因子(BDNF)修饰骨髓间充质干细胞(MSCs)对AD大鼠认知功能的改善作用。方法:采用双侧海马注射Aβ25-35制备AD大鼠模型,筛选40只雄性SD大鼠随机分为5组,假手术组(Sham组),AD模型组(AD组),移植骨髓MSCs治疗组(MSCs组),移植pIRESneo转染的骨髓MSCs治疗组(CON组)和移植pIRESneo-EGFP-BDNF转染的骨髓MSCs组(BDNF组),每组各8只。采用Morris水迷宫测试大鼠的学习记忆能力。结果:AD组与Sham组大鼠比较平均逃避潜伏期(AEL)延长、跨越平台次数明显减少(P<0.01),搜索策略明显差(P<0.01);MSCs组、CON组、BDNF组与AD组大鼠比较AEL明显缩短、跨越平台次数显著增加(P<0.05或P<0.01),搜索策略显著好转(P<0.01),且BDNF组与CON组、MSCs组大鼠比较改善更显著(P<0.05或P<0.01)。结论:经侧脑室移植BDNF修饰的骨髓MSCs可以显著改善AD大鼠的学习认知能力。

Objective： To investigate the improvement of learning and memory of Alzheimer＇s disease（AD） in rat model treated by brain-derived neurotrophic factor（BDNF） gene modified bone mesenchymal stem cells（MSCs） in jected through cerebral lateral ventricle.Methods： The AD rat models were constructed by injection of beta-amyloid peptide 25-35（Aβ25-35） into the hippocampus on both sides stereotaxically.Forty healthy male SD rats were selected and then randomly divided into five groups of eight each,i.e.sham operation group（Sham group）,AD rat model group（AD group）,bone MSCs group（MSCs group）,bone MSCs modified with pIRESneo plasmids group（CON group） and bone MSCs modified with pIRESneo-EGFP-BDNF plasmids group（BDNF group）.The learning and memory abilities of AD rat models were evaluated with Morris water maze test.Results： The average escape latency（AEL） was significantly prolonged and the frequency of crossing over the platform was significantly decreased and the searching strategy was poorer in AD group compared with Sham group（P〈0.01）.The AEL was significantly shortened,the frequency of crossing over the platform was significantly increased and the searching strategy was better in MSCs group,CON group,BDNF group respectively compared with those of AD group,and these behaviors were even more improved in BDNF group compared with those of MSCs group and CON group（P〈0.05 or P〈0.01）.Conclusion： The memory and learning of AD rat models were improved obviously with bone MSCs modified by plasmids carrying BDNF gene transplanted through cerebral lateral ventricle.