CAJ | 학술논문

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，H E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。目的：探討改良方法製備的血管性癡呆（VD ）模型的成模可信程度。方法採用間隔3 d 分2次結扎大鼠雙側頸總動脈法（改良2-VO ）與左側切口、不分離翼腭動脈的大鼠大腦中動脈梗死/再灌註法（改良MCAO/R）製備VD 模型，Morris水迷宮分彆進行定位航行實驗及空間探索實驗，通過逃避潛伏期、目標區域穿越次數及搜索策略測定各組大鼠的學習記憶能力，H E染色光學顯微鏡下觀察大鼠海馬組織CA1區組織結構的變化。結果術後20 d，與假手術組比較，兩模型組的大鼠逃避潛伏期均延長（P＜0．05），尤以改良2-VO組的逃避潛伏期最長；至術後41 d時改良MCAO/R組與假手術組無顯著性差異（P＞0．05），而改良2-VO組與假手術組始終具顯著性差異（P＜0．01），且此時兩模型組間比較差異也顯著（P＜0．01）。空間探索實驗，與假手術組比較，兩模型組分彆穿越平檯次數均減少，尤以改良2-VO組最為突齣；至術後第42天改良MCAO/R組與假手術組已無顯著性差異（P＞0．05）。且改良MCAO/R組術後第20天與第41天的潛伏期及術後第21天與第42天的穿越平檯次數比較，也均具有顯著性差異（P＜0．01）。搜索策略結果顯示，改良2-VO組遊泳軌跡多為邊緣式和隨機式，改良MCAO/R組通過訓練的增多搜索策略大部分改變為趨嚮式與直線式。兩模型組大鼠海馬CA1區組織結構均齣現細胞數目減少，細胞排列紊亂稀疏，細胞形態不完整，結構不正常，胞漿稀少，胞覈與胞漿界限模糊，細胞覈深染，固縮呈三角形或不規則形，覈仁不明顯，併齣現增生膠質細胞的現象。其中改良2-VO組最為嚴重，改良MCAO/R組較輕。結論兩種改良方法製作的VD 模型均可導緻大鼠齣現行為學及病理學的改變，其中改良2-VO模型更適用于較長時期的藥物療效研究，操作簡便，且模型穩定。而改良MCAO/R模型是較為理想的短期藥效研究或預防藥物療效研究的造模方法之一。
목적：탐토개량방법제비적혈관성치태（VD ）모형적성모가신정도。방법채용간격3 d 분2차결찰대서쌍측경총동맥법（개량2-VO ）여좌측절구、불분리익악동맥적대서대뇌중동맥경사/재관주법（개량MCAO/R）제비VD 모형，Morris수미궁분별진행정위항행실험급공간탐색실험，통과도피잠복기、목표구역천월차수급수색책략측정각조대서적학습기억능력，H E염색광학현미경하관찰대서해마조직CA1구조직결구적변화。결과술후20 d，여가수술조비교，량모형조적대서도피잠복기균연장（P＜0．05），우이개량2-VO조적도피잠복기최장；지술후41 d시개량MCAO/R조여가수술조무현저성차이（P＞0．05），이개량2-VO조여가수술조시종구현저성차이（P＜0．01），차차시량모형조간비교차이야현저（P＜0．01）。공간탐색실험，여가수술조비교，량모형조분별천월평태차수균감소，우이개량2-VO조최위돌출；지술후제42천개량MCAO/R조여가수술조이무현저성차이（P＞0．05）。차개량MCAO/R조술후제20천여제41천적잠복기급술후제21천여제42천적천월평태차수비교，야균구유현저성차이（P＜0．01）。수색책략결과현시，개량2-VO조유영궤적다위변연식화수궤식，개량MCAO/R조통과훈련적증다수색책략대부분개변위추향식여직선식。량모형조대서해마CA1구조직결구균출현세포수목감소，세포배렬문란희소，세포형태불완정，결구불정상，포장희소，포핵여포장계한모호，세포핵심염，고축정삼각형혹불규칙형，핵인불명현，병출현증생효질세포적현상。기중개량2-VO조최위엄중，개량MCAO/R조교경。결론량충개량방법제작적VD 모형균가도치대서출현행위학급병이학적개변，기중개량2-VO모형경괄용우교장시기적약물료효연구，조작간편，차모형은정。이개량MCAO/R모형시교위이상적단기약효연구혹예방약물료효연구적조모방법지일。
OBJECTIVE Toexplorethecredibityoftwoimprovedmodelsofsyntheticvascular dementia(VD)rats.METHODS OneimprovedmodelofVDratswasestablishedbyligatuingthebilat-eral 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 (i mproved MCAO/R). The learning and me mory ability was determined by escape latency in Morris water maze directional navi-gation test and cross-over ti mes in target areas in spatial probe test and the search strategy.The organi-zational structure in CA1 area of the hippocampus was observed and analyzed under a microscope after HEstaining.RESULTS Thelearningandmemoryabilitydecreasedsignificantlyin2modelgroupsat 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 nu mber of cells was reduced,their arrange ment was sparse and chaotic,the morphology of cells was inco mplete,the structure of cells was abnormal, cytoplasmwasscarce,andnucleoliwereinconspicuous.CONCLUSION TwoimprovedVDmodelscan lead to behavior and pathological changes in rats.The i mproved 2-VO model,si mple and stable,is suitable for drug efficacy research.The improved MCAO/R model is the ideal short-term efficacy study.