血管性痴呆大鼠海马区pro-BDNF、截短型BDNF、mBDNF的变化及与认知的关系

Changes of pro-BDNF, mature BDNF and truncated BDNF in hippocampus of vascular dementia rats

摘要:

目的  探讨血管性痴呆（VD）大鼠海马中脑源性神经营养因子前体蛋白（pro-BDNF）、成熟脑源性神经营养因子（mBDNF）、截短型脑源性神经营养因子（BDNF）变化及与认知功能的关系。方法  健康雄性SD大鼠120只，6月龄，体重350 g左右，随机分为模型组和假手术组，模型组结扎双侧颈总动脉，假手术组除不结扎血管外余同模型组，模型组和假手术组大鼠随机分为2、4、8和12周4个时间，水迷宫实验筛选造模成功大鼠，免疫组织化学法和Western blot检测假手术组及造模成功的大鼠不同时间点海马中pro-BDNF、mBDNF、截短型BDNF变化。结果  术后各时间点模型组大鼠的潜伏期均较假手术组延长（P <0.05）。免疫组织化学法检测显示模型组大鼠海马神经元形态改变、数量减少、BDNF表达下降。术后模型组pro-BDNF、mBDNF、截短型BDNF较假手术组降低（P <0.05），pro-BDNF水平下降趋势较缓慢，截短型BDNF水平下降趋势在缺血早期变化显著，后期变化缓慢；mBDNF水平下降趋势在缺血早期变化不明显，后期变化显著。结论  慢性缺血VD大鼠海马区pro-BDNF、mBDNF、截短型BDNF均有改变，3者比例的改变可能与VD大鼠认知功能障碍有关。

Abstract:

Objective To investigate the changes of pro-brain-derived neurotrophic factor (pro-BDNF), mature BDNF and truncated BDNF in hippocampus of vascular dementia rats. Methods A total of 120 healthy male Sprague -Dawley rats aged 6 months and weighting 350 g were randomly divided into model group and sham-operation group. The model of chronic cerebral ischemia was established by permanent occlusion of the bilateral common carotid arteries (2VO) in rats, while the sham-operation group accepted the same operation except occlusion of the bilateral common carotid arteries. The rats of both model group and sham-operation group were randomly divided into 2-week, 4-week, 8-week and 12-week sub-groups, and the behavior of the rats in each group was evaluated by the Morris water maze to select the successful modeling, then the brains were collected for immunohistochemistry and Western blot to detect the changes of pro-BDNF, mature BDNF and truncated BDNF in the hippocampus. Results The escape latency of the rats in the model group was significantly extended compared with the sham-operation group (P < 0.05). Compared with the sham-operation group, the total BDNF of the model group reduced gradually with the prolonged ischemic time, and the truncated BDNF in the model group significantly reduced in 4 weeks, 8 weeks and 12 weeks (P < 0.05), and pro-BDNF significantly reduced in 8 weeks and 12 weeks (P < 0.05), and mature BDNF significantly reduced in 12 weeks (P < 0.05). Conclusions Pro-BDNF, mature BDNF and truncated BDNF have changed in the hippocampus of chronic cerebral ischemia rats, and the change in the proportion of three isoforms of BDNF may be associated with cognitive dysfunction.