山茱萸环烯醚萜苷对血管性痴呆大鼠学习记忆能力及脑组织病理变化的影响

孟敏　杨翠翠　张丽

摘要：目的 觀察山茱萸环烯醚萜苷对血管性痴呆（VD）大鼠学习记忆能力和脑组织病理变化的影响，探讨其相关机制。方法 SD大鼠随机分为假手术组、模型组、阳性药组和山茱萸环烯醚萜苷低、中、高剂量组。采用永久性双侧颈总动脉结扎（2VO）手术造模，术后6 h开始灌胃给药，每日1次，共3个月。Morris水迷宫实验检测大鼠空间学习记忆能力，物体识别实验评价大鼠识别记忆能力。免疫组化染色检测脑组织存活神经元和胆碱乙酰基转移酶（ChAT）表达。结果 永久性2VO术后3个月，模型组大鼠逃避潜伏期延长，识别指数降低，海马和大脑皮层NeuN阳性神经元存活数减少，ChAT表达降低；与模型组比较，山茱萸环烯醚萜苷各剂量组大鼠逃避潜伏期缩短，识别指数升高，海马和大脑皮层NeuN阳性神经元存活数增多，海马ChAT表达升高。结论 山茱萸环烯醚萜苷通过保护神经元和促进ChAT表达从而改善VD大鼠的认知功能障碍。

关键词：山茱萸环烯醚萜苷；双侧颈总动脉结扎；血管性痴呆；认知功能障碍；神经元存活；胆碱乙酰基转移酶；大鼠

DOI：10.3969/j.issn.1005-5304.2018.06.014

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）06-0056-05

Effects of Cornel Iridoid Glycoside on Learning-memory Ability and Brain Pathological Changes in Vascular Dementia Rats

MENG Min， YANG Cui-cui， ZHANG Li， LI Ya-li， ZHANG Lan， LI Lin

Department of Pharmacy， Xuanwu Hospital of Capital Medical University， Beijing Engineering Research Center for Nervous System Drugs， Key Laboratory for Neurodegenerative Diseases of Ministry of Education， Beijing 100053， China

Abstract： Objective To investigate the effects of cornel iridoid glycoside （CIG） on the learning-memory ability and pathological changes in the brain of vascular dementia （VD） rats； To discuss relevant mechanism of action. Methods SD rats were randomly divided into sham-operation group， model group， positive medicine group， CIG groups low-， medium- and high-dose groups. The animal model of VD was replicated by permanent bilateral common carotid artery occlusion （2VO） in rats. Drugs were intragastrically administered 6 h after surgery and then once a day for 3 months. Morris water maze test was used to detect spatial learning-memory ability， and recognition memory was measured by the object recognition test. Immunohistochemical staining was used to detect the neuronal survival and the expression of choline acetyltransferase （ChAT） in the brain. Results Three months after permanent 2VO operation， the model rats showed a longer escape latency in Morris water maze， a lower discrimination index in the object recognition test， and a decrease in NeuN positive neuronal survival and ChAT expression in the hippocampus and cerebral cortex. Compared with the model group， intragastric administration of CIG for 3 months shortened the escape latency in Morris water maze， elevated the discrimination index in the object recognition test， and increased the NeuN positive neuronal survival in the hippocampus and cerebral cortex and ChAT expression of 2VO rats. Conclusion CIG can improve the cognitive impairment of VD model rats through protecting neurons and promoting ChAT expression.

Keywords： corneliridoid glycoside； bilateral common carotid artery ligation； vascular dementia； cognitive impairment； neuronal survival； choline acetyltransferase； rats

血管性痴呆（vascular dementia，VD）是由缺血性卒中、出血性卒中及造成记忆、认知和行为等脑区低灌注脑血管疾病所致的严重认知功能障碍综合征。大鼠永久性双侧颈总动脉结扎（bilateral common carotid artery ligation，2VO）致慢性脑血流灌注不足模型能很好地模拟人VD中认知功能障碍和神经元死亡等病理变化。山茱萸环烯醚萜苷（cornel iridoid glycoside，CIG）是从传统补肾中药山萸肉中提取的有效组分。……