血管性痴呆模型大鼠空间记忆障碍与海马CA1区神经元凋亡和乙酰胆碱释放有关

目的 探讨血管性痴呆（vascular dementia,VaD）模型大鼠海马乙酰胆碱（acetylcholine, ACh）含量与海马CAl区神经元凋亡以及空间记忆障碍的相关性.方法 40只健康雄性Sprague-Dawley大鼠随机分为VaD组和假手术组,每组20只.间断夹闭颈总动脉法建立VaD模型.微透析法采集大鼠海马区透析液,高效液相色谱分析检测透析液ACh含量.Morris水迷宫实验测试其空间记忆能力.TUNEL染色法检测海马CA1区神经元凋亡.结果 微透析分析显示,VaD组海马区ACh含量较假手术组显著性降低（0.442＆#177;0.028） μmmol/L对（1.560＆#177;0.092） μmmol/L；t=51.697,P=0.000].TUNEL染色显示,VaD组海马CA1区细胞凋亡率显著性高于假手术组（55.652＆#177;2.051）％对（6.530＆#177;1.872）％;t =79.114,P=0.000].不同检测时间点逃避潜伏期均显著性延长第3天时：（49.713＆#177;18.161）s对（13.322＆#177;2.454）s,t=-8.881,P=0.000）；第4天时：（34.368＆#177;7.424）s对（10.503＆#177;1.415）s,t=-14.121,P=0.000；第5天时：（30.676＆#177;6.669）s对（7.311＆#177;1.534）s,t=-15.270,P=0.000],穿越平台次数显著性减少（3.768＆#177;1.072）次对（10.218＆#177;1.165）次；=18.224;P=0.000].Pearson相关分析显示,VaD组海马ACh浓度与逃避潜伏期呈负相关（第3天时：r=-0.476,P=0.034；第4天时：r=-0.700,P=0.001；第5天时：r=-0.693,P=0.001）,与穿越平台次数呈正相关性（r=0.689,P=0.001）,与海马CA1区神经元凋亡率呈负相关（r=-0.271,P=0.031）.结论 VaD模型大鼠海马CA1区ACh含量降低,神经元凋亡率升高,可能是VaD大鼠认知损害的机制之一.

Spatial memory impairment is related to the neuronal apoptosis in the CA1 region of the hippocampus and the acetylcholine release in the rat model of vascular dementia

Objective To investigate the correlations between the hippocampal acetylcholine （ACh） content and neuronal apoptosis in the hippocampal CA1 region as well as the spatial memory impairment in a rat model of vascular dementia （VaD）.Methods Forty male healthy Sprague-Dawley rats were randomly divided into either a VaD group or a sham operation group （n =20 in each group）.A VaD model was induced by intermittently clipping common carotid artery.Microdialysis was used to collect dialysis solutions in rat hippocampus.High-performance liquid chromatographic analysis was used to detect the ACh content in the dialysis fluid.Morris water maze test was used to test their learning and memory abilities.TUNEL staining was used to detect neuronal apoptosis in the hippocampal CA1 region.Results Microdialysis analysis showed that the ACh content in the hippocampus in the VaD group was significantly lower than that in the sham operation group （0.442 ＆#177; 0.028 μmmol/L vs.1.560 ＆#177; 0.092 μ mmol/L; t =51.697,P =0.000）.TUNEL staining showed that the apoptosis rate in the hippocampal CA1 region in the VaD group was significantly higher than that in the sham operation group （55.652% ＆#177;2.051% vs.6.530% ＆#177; 1.872% ; t =79.114,P=0.000）.The escape latencies at different detection time points were prolonged significantly （At day 3：49.713 ＆#177; 18.161 s vs.13.322 ＆#177; 2.454 s; t =-8.881,P =0.000; at day 4：34.368 ＆#177; 7.424 s vs.10.503＆#177;1.415 s; t=-14.121,P=0.000; at day 5：30.676＆#177; 6.669s vs.7.311＆#177; 1.534 s; t=-15.270,P =0.000）,and the numbers of cross platform were reduced significantly （3.768 ＆#177; 1.072 vs.10.218 ＆#177; 1.165; t =18.224,P=0.000）.Pearson correlation analysis showed that the ACh contents in the VaD group were negatively correlated with the escape latencies （at day 3：r =-0.476,P =0.034; at day 4：r=-0.700,P=0.001; at day 5：r=-0.693,P=0.001）.They were positively correlated with the numbers of cross platform （r =0.689,P =0.001）,and negatively correlated with the neuronal apoptosis rates in the hippocampal CA1 region （r =-0.271,P =0.031）.Conclusions The decreased ACh content,the increased neuronal apoptosis rate in the rat hippocampal CA1 region in the VaD model may be one of the mechanisms of cognitive impairment in VaD rats.