机构地区:[1]中国中医科学院西苑医院,中国中医科学院老年病研究所,北京100091
出 处:《中药新药与临床药理》2020年第3期294-299,共6页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:北京市科学技术委员会G20工程创新研究项目-“十病十药”研发课题(Z171100001717016)。
摘 要:目的观察参麻益智方(SMYZ)对多发性脑梗塞致血管性认知障碍(VCI)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。方法健康Wistar大鼠,采用微血栓栓塞法制备多发性脑梗塞模型,手术成功后筛选致认知障碍的大鼠随机分成5组:模型对照组,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)。另设空白对照组、假手术组,每组各10只。灌胃给药,模型对照组、空白对照组和假手术组给予等体积蒸馏水灌胃,连续灌胃8周后进行相关指标检测。采用Morris水迷宫检测大鼠学习记忆能力;HE染色法观察海马CA1区病理形态学改变;酶联免疫法测定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)、丙二醛(MDA)、超氧化物歧化酶(SOD)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,模型对照组大鼠逃避潜伏期、总游泳路程、IL-1β、TNF-α含量、MDA含量均明显增加(P<0.01),穿越平台次数、目标象限路程占总路程百分比、目标象限时间占总时间百分比、GSH、SOD、GSH-PX含量均明显减少(P<0.05,P<0.01),海马CA1区发生明显病理形态学改变。与模型对照组比较,参麻益智方低、中、高剂量组大鼠逃避潜伏期、IL-1β含量均明显减少(P<0.05,P<0.01),SOD含量均明显增加(P<0.05,P<0.01),可改善海马CA1区的病理形态;参麻益智方中、高剂量组大鼠总游泳路程、TNF-α、MDA含量均明显减少(P<0.05,P<0.01),穿越平台次数、目标象限路程占总路程百分比、目标象限时间占总时间百分比、GSH、GSH-PX含量均明显增加(P<0.05,P<0.01)。结论参麻益智方对多发性脑梗塞致血管性认知障碍大鼠的学习记忆能力具有改善作用,并具有改善其海马组织的病理形态,抑制炎症反应,改善氧化应激状态的作用。Objective To investigate the influence of Shen Ma Yizhi decoction(SMYZ)on learning memory ability and serum inflammatory factors and oxidative stress in the model rats of multiple cerebral infarction induced vascular cognitive impairment(VCI).Methods The multiple cerebral infarction model was established by micro-thrombosis embolization in healthy Wistar rats.Rats confirmed to be cognitive impaired after surgery were randomly divided into 5 groups:Model group,Donepezil group(0.45 mg·kg^-1),SMYZ D group(2.97 g·kg^-1),SMYZ Z group(5.94 g·kg^-1),SMYZ G group(11.88 g·kg^-1);Control group and Sham group were also set up with 10 rats in each group.All of the medicine were given by gavage,Model group,Control group and Sham group were administered of equivalent distilled water.After continuous intragastric administration of 8 weeks,relevant indicators were examined.Morris water maze was used to detect rats’learning and memory abilities;HE staining was used to observe pathomorphological changes of hippocampal CA1;serum levels of inflammatory factor of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by Enzyme-Linked Immunosorbnent Assay;contents of glutathione(GSH),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by colorimetric method;content of glutathione peroxidase(GSH-PX)was measured by non-enzymatic immunoassay.Results Compared with Sham group,escape latency and total swimming distance of rats,serum levels of IL-1β,TNF-αand MDA increased significantly(P<0.01);the times across platform,percentage of target quadrant distance to total distance,and percentage of target quadrant time to total time,serum levels of GSH,SOD and GSH-PX decreased significantly(P<0.05,P<0.01),and significant pathmorphological changes in its hippocompus CA1 area in model group.Compared with model group,escape latency of rats and serum levels of IL-1βdecreased significantly(P<0.05,P<0.01),serum levels of SOD increased significantly(P<0.05,P<0.01),and improved the pathomorphology of its hippocampus i
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