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  

The effects of minocycline on spatial learning and memory ability and expression of BACE-1 and Aβ in hippocampaus in a rats with chronic cerebral hypoperfusion

作　　者：李国艳[1] 余昌胤[1] 杨华[2] 

机构地区：[1]遵义医学院第一附属医院神经内科,贵州遵义563003 [2]遵义医学院第一附属医院病理科,贵州遵义563003

出　　处：《中风与神经疾病杂志》2013年第2期115-119,共5页Journal of Apoplexy and Nervous Diseases

基　　金：贵州省卫生厅科技基金(gzwkj2010-1-050)

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(P<0.05,P<0.01),空间探索时间明显减少(P<0.01);治疗组潜伏期较模型组明显缩短(P<0.05,P<0.01),空间探索时间明显增加(P<0.05,P<0.01)。模型组BACE-1和Aβ的表达较假手术组明显增加(P<0.01),治疗组BACE-1和Aβ的表达较模型组显著降低(P<0.05,P<0.01)。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。Objective To observe the minocycline influences on learning and memory ability in rats with chronic cerebral hypoperfusion, and the expression of BACE-1, Aβ in brain. To he study provided an evidence for clinic treating cog- nitive impediment after chronic cerebral hypoperfusion. Methods Total 72 Sprague-Dawlay rats, randomly divided into 3 groups ： sham group （ n = 24 ） , CCH group （ n = 24 ） , minocycline group （ n = 24 ） , CCH group were followed occlusion of bi- lateral common carotid arteries （2-VO）. Minocyeline group were injected with minocycline （50mg/kg/d） after 2-VO on the base of CCH group,sham group and CCH group were injected with isodose saline. There were 3 observational time points in eachvery group：l st,2st,3st month later after operation with rats. Each group rats in each group were executed the latency of place navigation and spatial probe time （water maze test）. Then we dissected rat brain and the expression of BACE-1 ,Aβ in hippocampus wereas assayed by immunohistochemistry analysis. Results （1）At 1st, 2st, 3st month, compared with the sham group,CCH group＇s escape latency （EL） was improved significantly （P 〈 0. 05 ,P 〈 0.01 ）, spatial probe time was decreased significantly （P 〈 0.01 ）, spatial probe time was decreased significantly （ P 〈 0.01 ）. Compared with the CCH group,minocycline group＇ s escape latency （EL） in minocycline group was decreased significantly （P 〈 0.05, P 〈 0.01 ） , spatial probe time was improved significantly（ P 〈 0.05, P 〈 0.01 ）. （ 2 ） Compared with the sham group, the expression of BACE and Aβ in CCH group significantly increased （P 〈 0.01 ） , the expression of BACE and Aβ in minocycline group sig- nificantly decreased （P 〈 0.05 ,P 〈 0.01 ）. Conclusion Minocycline can improve the spatial learning ability and memory in rats with chronic cerebral hypoperfusion. Its the mechanism may be related to the inhibitedion of expression of BACE and Aβ in rats which iswith chroni

关 键 词：慢性脑低灌注 米诺环素 学习记忆能力 BACE-1 Β-淀粉样蛋白 

分 类 号：R743[医药卫生—神经病学与精神病学]