摘要目的:探讨黄芪甲甙是否通过缓解慢性脑缺血致血管性痴呆(VD)模型大鼠额叶皮层及海马的氧化应激损伤从而改善其空间学习和记忆能力。方法:将72只成年雄性Wistar大鼠按随机数字表法分为假手术组( n=12)、模型组( n=20)、黄芪甲甙10 mg组( n=20)、黄芪甲甙20 mg组( n=20)，后3组大鼠采用改良的双侧颈总动脉永久性结扎法制备成慢性脑缺血致VD模型，造模后3 h起分别腹腔注射等量生理盐水或10 mg/kg、20 mg/kg黄芪甲甙溶液，1次/d、共90 d。造模后第90~94天，采用Morris水迷宫实验测试各组大鼠的空间学习和记忆能力水平，然后应用酶联免疫吸附法(ELISA)检测大鼠额叶皮层及海马CA1区超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性及脂质过氧化产物丙二醛(MDA)含量，应用免疫组化染色检测4-羟基壬烯醛(4-HNE)、8-羟基脱氧鸟苷(8-OHdG)阳性细胞数。 结果:(1)在定位航行实验的第3、4、5天，模型组大鼠的逃避潜伏期明显长于假手术组，黄芪甲甙20 mg组大鼠的逃避潜期明显缩于模型组，差异均有统计学意义( P<0.05)。空间搜索实验显示模型组大鼠在原平台区域时间百分比(20.3%±1.7%)明显短于假手术组(48.2%±3.6%)，黄芪甲甙20 mg组大鼠在原平台区域时间百分比(39.7%±3.2%)明显长于模型组，差异均有统计学意义( P<0.05)。(2)与假手术组相比，模型组大鼠额叶皮层及海马CA1区SOD、GSH-Px、CAT活性下降，MDA含量升高，差异均有统计学意义( P<0.05)；与模型组相比，黄芪甲甙20 mg组大鼠额叶皮层及海马CA1区SOD、GSH-Px、CAT活性升高，MDA含量降低，差异均有统计学意义( P<0.05)。(3)与模型组相比，黄芪甲甙20 mg组大鼠额叶皮层及海马CA1区4-HNE、8-OHdG阳性细胞数明显减少，差异均有统计学意义( P<0.05)。 结论:腹腔注射高剂量黄芪甲甙可有效缓解慢性脑缺血大鼠额叶皮层及海马的氧化应激损伤并改善其空间学习和记忆能力。

abstractsObjective:To investigate whether astragaloside (AST) IV can improve spatial learning and memory abilities by alleviating oxidative stress damage to the frontal cortex and hippocampus in vascular dementia (VD) rats induced by chronic cerebral ischemia.Methods:Totally, 72 adult male Wistar rats were randomly assigned to four groups: sham-operated group ( n=12), model group ( n=20), AST-IV 10 mg group ( n=20), and AST-IV 20 mg group ( n=20); chronic cerebral ischemia-induced VD models in the later three groups were established by permanent bilateral common carotid artery occlusion (BCCAO); 3 h after BCCAO, these rats were administered with saline, 10 mg/kg AST-IV, or 20 mg/kg AST-IV once daily for a consecutive 90 d. Ninety-four d after modeling, spatial learning and memory abilities were assessed by Morris water maze; the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and malondialdehyde (MDA) levels were measured by enzyme linked immunosorbent assay (ELISA). The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal (4-HNE) and 8-hydroxy20-deoxyguanosine (8-OhdG), respectively. Results:(1) On the 3 rd, 4 th and 5 th d of place navigation test, the escape latency in rats of the model group was significantly longer than that in the sham-operated group, and that in the AST-IV 20 mg group was significantly shorter than that in the model group ( P<0.05); spatial probe test showed that the time percentage of rats spending in platform region in the model group (20.3%±1.7%) was significantly smaller than that in the sham-oprated group (48.2%±3.6%), and that in the AST-IV 20 mg group (39.7%±3.2%) was significantly larger than that in the model group ( P<0.05). (2) As compared with those in the sham-operated group, the SOD, GSH-Px and CAT activities were statistically decreased while MDA level was significantly increased in the frontal cortex and hippocampal CA1 area of rats in the model group ( P<0.05); as compared with those in the model group, the SOD, GSH-Px and CAT activities were statistically increased while MDA level was significantly decreased in the frontal cortex and hippocampal CA1 area of rats in the AST-IV 20 mg group ( P<0.05). (3) As compared with those in the model group, the numbers of 4-HNE and 8-oHdG positive cells in the frontal cortex and hippocampal CA1 area of rats in the AST-IV 20 mg group were significantly smaller ( P<0.05). Conclusion:Intraperitoneal injection of high dose AST-IV can ameliorate oxidative damage in the frontal cortex and hippocampal CA1 area in chronic cerebral ischemia-induced VD models, and has the potential to reverse spatial learning damages and memory dysfunction.