三氯化铝诱发阿尔茨海默病过程中熊果酸灌胃对大鼠认知功能的改善作用观察  

Improvement effect of ursolic acid on cognitive function in rats during the process of AlCl_(3)-induced Alzheimer's disease

作　　者：刘萍萍 肖一 张翼 何学芳 彭红 季一飞 LIU Pingping;XIAO Yi;ZHANG Yi;HE Xuefang;PENG Hong;JI Yifei(Department of Neurology,Nanchong Central Hospital(Beijing Anzhen Hospital Nanchong Central Hospital),Nanchong 637000,China)

机构地区：[1]南充市中心医院(北京安贞医院南充医院)神经内科四川省神经系统疾病临床医学研究中心,四川南充637000

出　　处：《山东医药》2024年第9期19-23,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81870966);四川省自然科学基金项目(2022NSFSC0756)。

摘　　要：目的观察三氯化铝(AlCl_(3))诱发阿尔茨海默病(AD)过程中熊果酸(UA)灌胃对大鼠认知功能的改善作用,并探讨其作用机制。方法24只雄性Wistar大鼠随机分为空白组、UA组、AlCl_(3)组、AlCl_(3)+UA组,每组6只。空白组大鼠灌胃生理盐水,UA组大鼠灌胃UA,AlCl_(3)组大鼠灌胃AlCl_(3)建立AD模型,AlCl_(3)+UA组大鼠灌胃AlCl_(3)诱发AD过程中灌胃UA。各组大鼠灌胃停止5 d后,采用Morris水迷宫实验观察大鼠认知功能。取各组大鼠,麻醉后断头处死大鼠,取大鼠大脑皮层和海马组织,采用分光光度法测定大鼠大脑皮层和海马组织中的铝含量,采用比色法检测各组大鼠大脑皮层和海马组织中乙酰胆碱酶(AChE)活性,测定各组大鼠大脑皮层和海马组织中氧化应激标志物超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)活性,并计算硫代巴比妥酸反应物(TBARS)活性,采用实时荧光定量PCR法检测各组大鼠大脑皮层和海马组织中炎症因子TNF-α、IL-6、NF-κB、COX-2 mRNA相对表达量。结果与空白组及UA组相比,AlCl_(3)组大鼠逃避潜伏期更长、在原平台所在象限停留时间更短(P均<0.05);与AlCl_(3)组相比,AlCl_(3)+UA组大鼠逃避潜伏期更短、在原平台所在象限停留时间更长(P均<0.05)。AlCl_(3)组大鼠大脑皮层和海马组织中的铝含量均高于其余各组(P均<0.05)。AlCl_(3)组大鼠大脑皮层和海马组织中的AChE活性均高于其余各组(P均<0.05)。AlCl_(3)组大鼠大脑皮层和海马组织中TBARS活性均高于其余各组,SOD、CAT、GSH活性均低于其余各组(P均<0.05)。AlCl_(3)组大鼠大脑皮层和海马组织中炎症因子TNF-α、IL-6、NF-κB、COX-2 mRNA相对表达量均高于其余各组(P均<0.05)。结论UA可改善AlCl_(3)诱导的AD模型大鼠的认知功能,其作用机制可能与降低大鼠大脑皮层和海马组织中铝含量、AChE活性、氧化应激水平和炎症因子的表达有关。Objective To observe the improvement effect of intragastric administration of ursolic acid(UA)on cog-nitive function in rats during the process of Alzheimer's disease(AD)induced by aluminium trichloride(AlCl_(3))and to ex-plore its mechanism.Methods Twenty-four male Wistar rats were randomly divided into the blank group(n=6),UA group(n=6),AlCl_(3)group(n=6)and AlCl_(3)+UA group(n=6),respectively.The rats in the blank group were given normal saline,the rats in the UA group were intragastrically administered AlCl_(3)to establish the AD models,and the rats in the Al-Cl_(3)+UA group were intragastrically given UA during the process of AD induced by AlCl_(3).After stopping intragastric admin-istration for 5 d,the cognitive function of rats in each group was observed by Morris water maze test.The rats in each group were killed by decapitation after anesthesia,and the cerebral cortex and hippocampus were taken.The aluminum content in the cerebral cortex and hippocampus was determined by spectrophotometry,and the activity of acetylcholinase(AChE)in the cerebral cortex and hippocampus was detected by colorimetry.The activity of superoxide dismutase(SOD),catalase(CAT)and glutathione(GSH)in cerebral cortex and hippocampus was measured,and the activity of thiobarbituric acid re-actants(TBARS)was calculated.The relative expression levels of inflammatory factors TNF-α,IL-6,NF-κB and COX-2 mRNA in cerebral cortex and hippocampus were detected by real-time fluorescence quantitative PCR.Results Com-pared with the blank group and the UA group,the escape latency was longer and the stay time in the original platform quad-rant was shorter in the AlCl_(3)group(both P<0.05).Compared with the AlCl_(3)group,the escape latency was shorter and the stay time in the original platform quadrant was longer in the AlCl_(3)+UA group(both P<0.05).The content of aluminum in cerebral cortex and hippocampus in the AlCl_(3)group was higher than that in the other groups(P<0.05).The activity of AChE in cerebral cortex and hippocampus in the AlCl_(3)gr

关 键 词：熊果酸 阿尔茨海默病 三氯化铝 乙酰胆碱酯酶 氧化应激 神经炎症 动物实验 

分 类 号：R741[医药卫生—神经病学与精神病学]