参麻益智方对慢性脑缺血致血管性认知障碍大鼠学习记忆功能的干预作用  

Intervention of Shenma Yizhi Prescription on Learning and Memory in Rats with Vascular Cognitive Impairment Induced by Chronic Cerebral Ischemia

作　　者：孙成成[1,2] 刘剑刚 刘美霞[1,3] 罗增刚[3,4] 李浩[1,3] SUN Cheng-cheng;LIU Jian-gang;LIU Mei-xia;LUO Zeng-gang;LI Hao(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Graduate School of China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Geriatrics,China Academy of Chinese Medical Sciences,Beijing 100091,China;Beijing Administration of Traditional Chinese Medicine,Beijing 100053,China)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]中国中医科学院研究生院,北京100700 [3]中国中医科学院老年病研究所,北京100091 [4]北京市中医药管理局,北京100053

出　　处：《中国实验方剂学杂志》2020年第19期153-159,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：北京市G20工程创新研究科技计划项目“十病十药”研发课题(Z171100001717016)。

摘　　要：目的:观察参麻益智方对双侧颈总动脉结扎造成慢性脑缺血致血管性认知障碍模型大鼠的学习记忆能力和血清炎症因子及氧化应激相关指标的影响。方法:SPF级SD大鼠,采用双侧颈总动脉结扎法制备慢性脑缺血模型,手术成功后筛选认知障碍的大鼠按随机数字表法分成5组,模型组、盐酸多奈哌齐组(0.45 mg·kg^-1),参麻益智方低、中、高剂量组(2.97,5.94,11.88 g·kg^-1),另设假手术组,每组10只。给药方式为灌胃,其中模型组和假手术组给予等体积纯净水灌胃,连续灌胃8周后进行相关指标检测。采用Morris水迷宫实验进行大鼠学习记忆功能检测;苏木素-伊红(HE)染色观察海马CA1区病理形态学改变;比色法检测血清中乙酰胆碱(Ach),乙酰胆碱酯酶(AChE)含量;酶联免疫吸附测定(ELISA)检测大鼠血清炎症因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量;比色法检测谷胱甘肽(GSH),超氧化物歧化酶(SOD),丙二醛(MDA)含量;非酶促免疫法检测谷胱甘肽过氧化物还原酶(GSH-Px)含量。结果:与假手术组比较,模型组大鼠逃避潜伏期均明显增加,寻台次数、穿越原平台次数、原平台象限游泳时间占总游泳时间百分比均明显减少(P<0.05,P<0.01),Ach,GSH,GSH-Px含量均明显减少,AChE,IL-1β,TNF-α,MDA含量均明显增加(P<0.05,P<0.01);与模型组比较,参麻益智方低、中、高剂量组大鼠逃避潜伏期均显著减少,大鼠寻台次数、穿越原平台次数、原平台象限游泳时间占总游泳时间百分比均明显增加(P<0.05,P<0.01),参麻益智方中、高剂量组AChE含量显著减少(P<0.01),参麻益智方高剂量组大鼠血清Ach含量明显增加(P<0.05),大鼠血清IL-1β,TNF-α,MDA含量均明显减少(P<0.05,P<0.01),GSH,SOD,GSH-Px含量明显增加(P<0.05,P<0.01)。结论:参麻益智方可改善双侧颈总动脉结扎引起慢性脑缺血致血管性认知障碍大鼠的学习记忆能力,并具有改善其海马的病理形态Objective:To observe the effects of Shenma Yizhi prescription(SMYZ)on learning and memory,inflammatory factors and oxidative stress related indexes of rats with chronic cerebral ischemia inducing vascular dementia caused by bilateral common carotid artery ligation.Method:The chronic cerebral ischemia model of SPF grade SD rats was prepared by bilateral common carotid artery ligation.After successful surgery,the rats with cognitive impairment were randomly divided into 5 groups,model,donepezil(0.45 mg·kg^-1),SMYZ-low,medium and high dose(2.97,5.94,11.88 g·kg^-1),with 10 rats in each group,and 10 rats in sham operation group were established.Intragastric administration were given for 8 weeks respectively then followed Morris water maze test.The pathomorphological changes of hippocampus CA1 were observed.The serum levels of acetylcholine(Ach)and acetylcholinesterase(AChE)were detected,and the levels of inflammatory cytokines interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the serum of rats were detected.The contents of glutathione(GSH),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase reductase(GSH-Px)were observed.Result:Compared with sham operation group,the escape latency increased significantly in the model group,and the frequency of platform search,the frequency of crossing the original platform and the percentage of swimming time in the original platform quadrant decreased significantly(P<0.05,P<0.01).The contents of Ach and the contents of GSH and GSH-Px were significantly decreased(P<0.05,P<0.01).The contents of AChE,IL-1β and TNF-α and the contents of MDA were significantly increased(P<0.05,P<0.01).Compared with model group,the escape latency of rats in the in the low,medium and high dose groups of SMYZ prescription was significantly reduced(P<0.05,P<0.01).The frequency of looking for a platform,the frequency of crossing the original platform and the percentage of swimming time in the original platform quadrant of the rats in the low,medium and high dose groups of SM

关 键 词：参麻益智方 双侧颈总动脉结扎 血管性认知障碍 炎症因子 氧化应激 

分 类 号：R2-0[医药卫生—中医学] R289