米诺环素对慢性脑低灌注大鼠空间学习记忆能力及海马BACE-1和Aβ表达的影响

发布时间：2018-10-26 14:11

【摘要】：目的观察米诺环素对慢性脑低灌注大鼠空间学习记忆能力及海马BACE-1和Aβ表达的影响,为慢性脑低灌注认知功能障碍的治疗提供依据。方法 72只SD大鼠随机分为假手术组、慢性脑低灌注组、米诺环素治疗组。结扎双侧颈总动脉建立大鼠慢性脑低灌注模型,米诺环素治疗组在慢性脑低灌注模型的基础上连续给予50mg/kg/d的米诺环素灌胃。观察时间点分别为造模后1个月、2个月和3个月。采用Morris水迷宫对大鼠进行定位航行潜伏期和空间探索时间检测后,断头取脑,采用免疫组织化学法检测海马区脑组织BACE-1和Aβ。结果在造模后1个月、2个月和3个月时间点,模型组定位航行潜伏期较假手术组明显延长(P0.05,P0.01),空间探索时间明显减少(P0.01);治疗组潜伏期较模型组明显缩短(P0.05,P0.01),空间探索时间明显增加(P0.05,P0.01)。模型组BACE-1和Aβ的表达较假手术组明显增加(P0.01),治疗组BACE-1和Aβ的表达较模型组显著降低(P0.05,P0.01)。结论米诺环素能改善慢性脑低灌注大鼠空间学习记忆能力,其作用机制可能与其抑制慢性脑低灌注大鼠BACE-1的表达,减少Aβ的产生有关。
[Abstract]:Objective to observe the effects of minocycline on spatial learning and memory ability and the expression of BACE-1 and A 尾 in hippocampus of rats with chronic cerebral hypoperfusion. Methods 72 SD rats were randomly divided into sham-operation group, chronic cerebral hypoperfusion group and minocycline treatment group. The rat model of chronic cerebral hypoperfusion was established by ligating bilateral common carotid artery. Minocycline group was treated with minocycline (50mg/kg/d) on the basis of chronic cerebral hypoperfusion model. The observed time points were 1 month, 2 months and 3 months after modeling. Morris water maze was used to detect the latency of navigation and the time of space exploration in the rats. After the brain was cut off, the contents of BACE-1 and A 尾 in the hippocampus were detected by immunohistochemical method. Results at the time points of 1 month, 2 months and 3 months after modeling, the latency of positioning navigation in the model group was significantly longer than that in the sham operation group (P0.05, P0.01), and the time of space exploration was significantly reduced (P0.01). Compared with the model group, the latent period of the treatment group was significantly shorter (P0.05 / P0.01), and the time of space exploration was significantly increased (P0.05 / P0.01). The expression of BACE-1 and A 尾 in the model group was significantly higher than that in the sham operation group (P0.01), and the expression of BACE-1 and A 尾 in the treatment group was significantly lower than that in the model group (P0.05, P0.01). Conclusion minocycline can improve the spatial learning and memory ability of rats with chronic cerebral hypoperfusion, and its mechanism may be related to the inhibition of BACE-1 expression and the reduction of A 尾 production in chronic cerebral hypoperfusion rats.
【作者单位】：遵义医学院第一附属医院神经内科;遵义医学院第一附属医院病理科;
【基金】：贵州省卫生厅科技基金(gzwkj2010-1-050)
【分类号】：R965

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