新型脑白质病变动物模型及其脑小血管的病理学研究

目的建立一个新型的具有高血压及脑小血管病理改变的脑白质病变(white matter lesions,WMLs)动物模型。方法 13只雄性Sprague-Dawley大鼠,随机分为假手术组(n=6)与易卒中型肾血管性高血压-改良的2VO组(stroke-prone renovascular hypertensive rat-modified 2 vessel occlusion RHRSP/Modified 2VO)(n=7),RHRSP/Modified 2VO组先行双肾双夹术制作RHRSP模型,12周后间隔1周先后夹闭双侧颈总动脉。双肾双夹术后20周对大鼠进行水迷宫试验观察大鼠是否存在空间记忆功能的受损,组织病理学检测观察是否存在脑白质病变及相应的脑小血管病理学改变。结果双肾双夹术后12周,RHRSP/Modified 2VO组7只大鼠收缩压均大于180 mm Hg;水迷宫实验:RHRSP/Modified 2VO组的逃避潜伏期较假手术组明显升高(P0.05),穿越平台次数及原平台象限停留时间比较假手术组明显降低(2.5±1.05 vs.5±1.67);(28.04%±14.13%vs.49.69%±13.12%)],差异具有统计学意义(P0.05);RHRSP/Modified 2VO组脑白质病变的分级明显高于假手术组(2.17±0.75 vs.0.33±0.52),差异具有统计学意义(P0.05),且RHRSP/Modified 2VO大鼠存在脑小血管的病理改变(小动脉管壁增厚、血脑屏障破坏及静脉胶原沉积)。结论 RHRSP/Modified 2VO是适用的WMLs动物模型,可用于探究WMLs的发病机制及治疗靶点。

Establishment of a novel animal model for white matter lesions and its pathological study of cerebral small vessels

Objective To establish a novel white matter lesions (WMLs) animal model with hypertension and to ex?amine its pathological changes of cerebral small vessels. Methods Thirteen male Sprague-Dawley rats were randomly di?vided into sham operation group (n=6) and stroke-prone renovascular hypertensive rat-modified 2 vessel occlusion group (RHRSP/Modified 2VO)(n=7). RHRSP/Modified 2VO group was induced by the two-kidney two clip method first and un?derwent the operation of modified bilateral common carotid artery occlusion (1 week interval ) 12 weeks later. Morris wa?ter maze test was used to detect spatial memory function and pathology test was used to investigate white matter lesions and the cerebral small vessels after 20 weeks of two-kidney two clip operation. Results Twelve weeks after two-kidney two clip operation, the blood pressure was more than 180mmHg in all RHRSP/Modified 2VO. Morris water maze test showed that escape latencies was significantly higher in RHRSP/Modified 2VO group than in the sham operation group (P<0.05). The number of crossing hidden platform as well as time ratio in the target quadrant of were significantly shorter in the RHRSP/Modified 2VO group than in sham operation group (2.5 ± 1.05 vs. 5 ± 1.67);(28.04 ± 14.13% vs. 49.69 ± 13.12%)](P<0.05). Compared to sham operation group, RHRSP/Modified 2VO group had a higher grade of WMLs (2.17± 0.75 vs.0.33 ± 0.52) (P<0.05) and exhibited the pathological changes of cerebral small vessels including small artery wall thickening, BBB disruption and venous collagen deposition. Conclusions RHRSP/Modified 2VO can be regarded as ap?propriate WMLs animal model and may therefore be adapted to explore pathogenesis and possible treatments for WMLs.