中文摘要：

目的探讨脑源性生长因子（BDNF）组蛋白H3乙酰化修饰在阿尔茨海默病（AD）发病机制中的作用。方法选用2月龄和8月龄SAMP8小鼠作为AD动物模型，同月龄SAMR1小鼠作为对照组。应用水迷宫模型探索记忆损伤，同时使用蛋白印迹（Western blot）和染色质免疫共沉淀（CHIP）探索不同月龄小鼠的BDNF蛋白水平及组蛋白H3乙酰化调节变化。结果水迷宫测试显示，8月龄SAMP8小鼠穿越目标平台的次数[（0．9±0．4）次]显著低于2月龄SAMP8小鼠[（3．7±0．9）次]和8月龄SAMR1小鼠[（3．3±0．6）次]，差异有统计学意义（P〈0．05）；与2月龄SAMP8小鼠[（23．9±4．0）s]和8月龄SAMR1小鼠[（21．5±2．3）s]相比，8月龄SAMP8小鼠在目标象限停留时间[（11．7±2．8）S]显著降低，差异有统计学意义（P〈0．05）。Western blot结果显示，8月龄SAMP8小鼠海马BDNF蛋白表达水平与2月龄SAMP8小鼠和8月龄SAMR1小鼠相比显著降低（P〈0．05）；CHIP实验发现，与2月龄SAMP8小鼠和8月龄SAMR1小鼠相比，8月龄SAMP8小鼠海马BDNF基因外显子IV和VI的启动子区域组蛋白H3乙酰化结合水平显著下调（P〈O．05）；各组小鼠海马脑区BDNF基因外显子I和III启动子区域组蛋白H3乙酰化的结合水平差异无统计学意义（P〉0．05）。结论AD发病过程中海马脑区BDNF基因IV和VI启动子区域组蛋白H3乙酰化修饰水平降低，这一异常的表观遗传学修饰过程可能是导致AD记忆损伤的机制之一。

英文摘要：

Objective To explore the role of histone H3 acetylation modification of brain derived neurotrophie factor （BDNF） in the pathogenesis of Alzheimer＇s disease （AD）.Methods 2 months and 8 months SAMP8 mice were used as AD model. Morris water maze was used to detect the impairment of learning and memory. Western blot was used to detect BDNF protein expression in the hippocampus, and chromatin immunoprecipitation （CHIP） was applied to study the changes of histone H3 aeetylation in different BDNF promoters. Results The results of water maze test showed that the time across the target quadrant in 8 months SAMP8 mice（0.9±0.4） was significant declined compared with that of 2 months SAMP8 mice（ 3.7 ±0.9） and 8 months SAMR1 mice （ 3.3 ± 0.6） （ all P〈 0.05 ）. Meanwhile, compared with 2 months SAMP8 mice（ （23.9±4.0） s ） and 8 months SAMR1 mice （ （ 21.5 ± 2.3 ） s ） , target quadrant time in the 8 months SAMP8 mice（（11.7±2.8） s） was also significantly reduced（both P〈0.05）. The western blot showed the expression of BDNF in the hippocampus of 8 months SAMP8 mice was significantly decreased compared with that of 2 months SAMP8 mice and 8 months SAMR1 mice（P〈0.05）. Lastly, CHIP assays showed that histone H3 acetylation of BDNF exon IV and VI in the hippocampus of 8 months SAMP8 mice were remarkably decreased（P〈0.05） compared with that of 2 months SAMP8 mice and 8 months SAMR1 mice. There was no significant change of histone H3 acetylation of BDNF exon I and III among all groups（P〉0.05）. Conclusion Histone H3 acetylation of BDNF exon IV and VI is reduced during the development of AD ,which may be the mechanism underlying the impairment of learning and memory in AD.