目的探讨改良方法制备的血管性痴呆(VD)模型的成模可信程度。方法采用间隔3 d分2次结扎大鼠双侧颈总动脉法(改良2-VO)与左侧切口、不分离翼腭动脉的大鼠大脑中动脉梗死/再灌注法(改良MCAO/R)制备VD模型,Morris水迷宫分别进行定位航行实验及空间探索实验,通过逃避潜伏期、目标区域穿越次数及搜索策略测定各组大鼠的学习记忆能力,HE染色光学显微镜下观察大鼠海马组织CA1区组织结构的变化。结果术后20 d,与假手术组比较,两模型组的大鼠逃避潜伏期均延长(P〈0.05),尤以改良2-VO组的逃避潜伏期最长;至术后41 d时改良MCAO/R组与假手术组无显著性差异(P〉0.05),而改良2-VO组与假手术组始终具显著性差异(P〈0.01),且此时两模型组间比较差异也显著(P〈0.01)。空间探索实验,与假手术组比较,两模型组分别穿越平台次数均减少,尤以改良2-VO组最为突出;至术后第42天改良MCAO/R组与假手术组已无显著性差异(P〉0.05)。且改良MCAO/R组术后第20天与第41天的潜伏期及术后第21天与第42天的穿越平台次数比较,也均具有显著性差异(P〈0.01)。搜索策略结果显示,改良2-VO组游泳轨迹多为边缘式和随机式,改良MCAO/R组通过训练的增多搜索策略大部分改变为趋向式与直线式。两模型组大鼠海马CA1区组织结构均出现细胞数目减少,细胞排列紊乱稀疏,细胞形态不完整,结构不正常,胞浆稀少,胞核与胞浆界限模糊,细胞核深染,固缩呈三角形或不规则形,核仁不明显,并出现增生胶质细胞的现象。其中改良2-VO组最为严重,改良MCAO/R组较轻。结论两种改良方法制作的VD模型均可导致大鼠出现行为学及病理学的改变,其中改良2-VO模型更适用于较长时期的药物疗效研究,操作简便,且模型稳定。而改良MCAO/R模型是较为理想的短期药效研究或预防药物疗效研究的造模方法之一。
OBJECTIVE To explore the credibity of two improved models of synthetic vascular dementia( VD) rats. METHODS One improved model of VD rats was established by ligatuing the bilateral common carotid artery twice at 3 d( improved 2-VO),while the other was established by blocking the middle cerebral artery on the left side by separating pterygopalatine arteria( improved MCAO /R). The learning and memory ability was determined by escape latency in Morris water maze directional navigation test and cross-over times in target areas in spatial probe test and the search strategy. The organizational structure in CA1 area of the hippocampus was observed and analyzed under a microscope after HE staining. RESULTS The learning and memory ability decreased significantly in 2 model groups at 20 d after the operation. The escape latency was much longer in improved 2-VO group and improved MCAO /R group than that in sham group( P〈0. 05) especially in improved 2-VO group. 41 d after the operation,no difference between MCAO /R and sham group( P〈0. 05). The differences between improved 2-VO group and sham group remained significant( P〈0. 01),and difference between improved 2-VO group and improved MCAO /R group was significant( P〈0. 01) at 41 d. The cross-over times in the target area in spatial probe test decreased more significantly in 2 model groups than in sham group. 41 d after the operation,improved MCAO /R group was not different from sham group( P〈0. 05). Search strategy results showed that swimming trajectory in the improved 2-VO groupwas mostly edge and random type,but was of tendency type and straight type in the improved MCAO /R group. In the organization structure of hippopal CA1 area of rats,the number of cells was reduced,their arrangement was sparse and chaotic,the morphology of cells was incomplete,the structure of cells was abnormal, cytoplasm was scarce,and nucleoli were inconspicuous. CONCLUSION Two improved VD models can lead to behavior and pathological changes in rats. The