黄芪甲甙对慢性脑缺血致VD模型大鼠空间学习和记忆能力的改善作用及其机制研究  

Effect of astragaloside IV on improvement of spatial learning and memory abilities and its mechanism in v ascular dementia rat models of chronic cerebral ischemia

作　　者：张广林 李天晓[1] 常晓战 行君[1] Zhang Guanglin;Li Tianxiao;Chang Xiaozhan;Xing Jun(Department of Cerebrovascular Disease,Henan Provincial People's Hospital Affiliated to Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属河南省人民医院脑血管科,郑州450000

出　　处：《中华神经医学杂志》2020年第8期787-793,共7页Chinese Journal of Neuromedicine

摘　　要：目的探讨黄芪甲武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只成年维性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10mg组(n=20)、黄芪甲甙20mg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3h起分别腹腔注射等量生理盐水或10mg/kg.20mgkg黄芪甲甙溶液,1次/d.共90d。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-羟基王烯醛(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20mg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20mg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CAI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20mg组大鼠额叶皮层及海马CAI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,黄芪甲试20mg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。Objective 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,thesc rats were administered with saline,10 mgkg AST-IV,or 20 mgkg 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",4h and 5"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 CAI 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 we

关 键 词：黄芪甲甙 血管性痴呆 慢性脑缺血 氧化应激损伤 空间学习和记忆能力 

分 类 号：R285.5[医药卫生—中药学]