摘要
目的探讨汉黄芩素对慢性脑缺血大鼠行为学的影响和可能机制。方法大鼠随机分为假手术组、汉黄芩素干预组和磷酸盐缓冲液(phosphate buffered solution,PBS)对照组。采用二血管闭塞法制作慢性脑缺血大鼠模型。模型制作后6周,汉黄芩素干预组和PBS对照组分别给予汉黄芩素(50μmol/L,10ml/kg,1次/d)和等体积PBS灌胃,共14d。采用Morris水迷宫实验评价空间学习和记忆功能,激光共聚焦三维血管成像检测缺血脑组织血管增殖,5-溴脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine,BrdU)免疫组化染色检测脑缺血区细胞增殖情况,透射电镜检测缺血区神经细胞形态学变化。结果Morris水迷宫实验(n=8)显示,汉黄芩素干预组训练第2至第5天的逃避潜伏期分别为(43.45±8.64)s、(37.12±1.31)s、(34.75±5.36)s和(24.36±5.43)s,显著性短于PBS对照组的(51.69±5.32)s、(43.65±9.21)s、(50.19±10.31)s和(53.65±7.15)s(P均〈0.05);汉黄芩素干预组第一象限游泳时间较PBS对照组显著延长[(26.16±3.29)S对(14.38±2.16)s;P〈0.01]。激光共聚焦三维血管成像检测(n=4)显示,与PBS对照组比较,汉黄芩素干预组脑缺血区毛细血管内径显著缩小[(3.02±0.21)μm对(3.35±0.18)μm;P〈0.05],血管密度显著增高[(205.80±12.70)/0.002mm^3对(158.42±10.92)/0.002mm^3;P〈0.01],微血管总面积显著增加[(83389±4026)μm^2/0.002mm^3对(73349±3986)μm^2/0.002mm^3;P〈0.01]。免疫组化染色(n=6)显示,汉黄芩素干预组缺血脑组织BrdU阳性细胞数量较PBS对照组显著增多[(24.62±3.25)个/高倍视野对(9.87±2.89)个/高倍视野;P〈0.01]。透射电镜观察显示,汉黄芩素干预组细胞间隙炎性水肿较PBS对照组明显减轻。结论汉黄芩素可显著改善慢
Objective To investigate the effect of wogonin on ethology and its possible mechanisms in chronic cerebral ischemia in rats. Methods Rats were randomly divided into a sham operation group, a wogonin intervention group, and a phosphate buffered solution (PBS) control group. A rat model of chronic cerebral ischemia was induced by the two-vessel occlusion method. Six weeks after modeling, the rats in the wogonin intervention group and the PBS control group were intragastric administrated with wogonin (50 μmol/L, 10 ml/kg, once a day) and PBS with equal volume for 14 days. Morris water maze test was used to evaluate the spatial learning and memory function. Laser confocal three-dimensional vascular imaging was used to detect the vascular proliferation of ischemic brain tissue. 5-Bromo-2-deoxyuridine (BrdU)immunochemical staining was used to detect the cell proliferation in ischemic brain tissue. Transmission electron microscope was used to observe the morphological changes of neural cells in cerebral ischemic region. Results The Morris water maze (n =8) showed that the trains of escape latency from the second to the fifth day in the wogonin intervention group were 43.45 ± 8.64 s, 37. 12 ±1.31 s, 34. 75 ± 5.36 s, and 24.36 ± 5.43 s, respectively. They were significantly shorter than 51.69 ± 5.32 s, 43.65 ± 9. 21 s, 50. 19 ± 10. 31 s, and 53.65 ±7. 15 s in the PBS control group (all P 〈0. 05). The first quadrant swimming time of the wogonin intervention group was significantly longer than that of the PBS control group (26. 16 ± 3.29 s vs. 14. 38 ±2. 16 s; P〈0. 01). Laser confocal three-dimensional vascular imaging (n =4) showed that the capillary inner diameter in cerebral ischemia region of the wogonin intervention group was reduced significantly compared to the PBS control group (3.02 ±0. 21 μm vs. 3.35 ±0. 18 μm; P 〈0. 05), vascular density was increased significantly (205.80± 12.70/0. 002mm^3vs. 158.42± 10. 92/0. 002 mm^3; P〈 0. 01), and total microvascul
出处
《国际脑血管病杂志》
北大核心
2014年第9期660-664,共5页
International Journal of Cerebrovascular Diseases
基金
湖北省自然科学基金(2012FFB04330)
关键词
脑缺血
认知障碍
迷宫学习
记忆
黄烷酮类
汉黄芩素
新生血管化
生理性
神经保护药
大鼠
Brain Ischemia
Cognition Disorders
Maze Learning
Memory
Flavanones
Wogonin
Neovascularization, Physiologic
Neuroprotective Agents
Rats