BCL2L12基因治疗对于小鼠阿尔兹海默病的影响及机制

BCL2L12 Gene Treatment for Alzheimer's Disease in Mice

目的观察BCL2L12基因治疗对于阿尔茨海默病模型小鼠行为学及分子病理学的影响。方法应用立体定向仪将携带空壳基因及BCL2L12基因的腺相关病毒注射至C57小鼠海马CA1区,2周后相同部位注射Aβ(1μg),2周后进行行为学实验及免疫组织化学染色(6E10及AT8)。结果旷场实验发现,空壳基因治疗组与目的基因治疗组在中心区的时间与记录总时间的比值显著低于空白对照小鼠,两治疗组之间差异无统计学意义。水迷宫实验发现,目的基因治疗组及空白对照组平均潜伏期均于第2天显著缩短,而空壳基因治疗组平均潜伏期于第3天显著缩短。6E10及AT8免疫荧光染色发现空壳基因治疗组及目的基因治疗组小鼠染色脑片平均吸光度显著高于空白对照组小鼠,空壳基因治疗组小鼠染色脑片平均吸光度高于目的基因治疗组小鼠,但差异无统计学意义。结论应用BCL2L12基因治疗无法改善AD小鼠的焦虑情绪,但是可以提高AD小鼠的学习记忆功能,可能与BCL2L12基因治疗减少Aβ沉积以及Tau蛋白磷酸化有关。

Objective To investigate the BCL2L12 gene treatment for Alzheimer＇s disease（AD）in mice and the underlying mechanism.Methods Adeno-associated viruses carrying BCL2L12 gene or not were injected into the hippocampal CA1 region of C57 mice by using the stereotactic instrument.Aβ（1μg）was injected into the same regions 2weeks later.The water maze test,open field test,and immunohistochemical studies（antibody 6E10 and AT8）were performed at this time.Results The open field test showed that the ratio of time in the central area to the total observed time was significantly shorter in the BCL2L12 gene treatment group and blank gene treatment group than in the blank control group,and there was no significant difference between the two treatment groups.The water maze test revealed that the average latency time was markedly shortened on day 2in the blank control group and the BCL2L12 gene treatment mice but on day 3 in the blank gene treatment group.Immunofluorescence study with 6E10 and AT8antibody showed that the fluorescence intensity was significantly higher in the two treatment mice groups than that in the blank control group.Although the fluorescence intensity in the BCL2L12 gene treatment group was lower than that in the blank gene treatment group,there was no significant difference between them.Conclusion BCL2L12 gene treatment can not improve the anxiety of AD mice.However,it can increase the learning and memory capacity of AD mice,which is possibly associated with a decrease in Aβdeposition and Tau phosphorylation.