丁苯酞对糖尿病小鼠海马突触可塑性及氧化应激状态的影响  

Effect of butyphthalide on synaptic plasticity and oxidative stress in hippocampus of diabetes mellitus mice

作　　者：高明[1] 冀素晓 李杰[1] 康宁琳 张力辉[1] 张松筠[1] Gao Ming;Ji Suxiao;Li Jie;Kang Ninglin;Zhang Lihui;Zhang Songyun(Department of Endocrinology,Hebei Medical University No.2 Hospital,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]河北医科大学第二医院内分泌科,石家庄050000 [2]邯郸市第一医院内分泌科

出　　处：《中华老年心脑血管病杂志》2019年第11期1203-1206,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：河北省自然科学基金(H2018206320);河北省卫生和计划生育委员会科研基金(20180323)

摘　　要：目的观察丁苯酞对糖尿病小鼠海马突触可塑性和氧化应激状态的影响,探索丁苯酞保护糖尿病认知功能的作用机制。方法选取16只db/db小鼠随机分为糖尿病组和丁苯酞组,每组8只,另选取同窝db/m小鼠8只为对照组。丁苯酞组给予丁苯酞灌胃6周,糖尿病组等量植物油灌胃,对照组等量植物油灌胃。Morris水迷宫记录逃避潜伏期和目标象限自由游泳时间检测干预后学习和空间记忆功能;透射电子显微镜观察海马突触超微结构变化;ELISA检测海马超氧化物歧化酶(SOD)、丙二醛和8-羟化脱氧鸟苷(8-OHdG)水平;实时定量PCR和蛋白免疫印迹检测突触素、p67phox、gp91phox mRNA和蛋白表达。结果与对照组比较,糖尿病组和丁苯酞组第5天逃避潜伏期明显延长,目标象限自由游泳时间明显减少(P<0.05)。与糖尿病组比较,丁苯酞组逃避潜伏期明显减少,目标象限自由游泳时间明显增加(P<0.05),海马CA1区突触间隙结构较清晰、突触和囊泡数量增加,SOD水平明显上升(P<0.05),丙二醛、8-OHdG水平明显下降[(1.02±0.04)ng/L vs(1.35±0.11)ng/L,(18.94±0.45)ng/L vs(22.19±0.34)ng/L,P<0.05],突触素表达明显升高,p67phox和gp91phox表达明显降低(P<0.05)。结论丁苯酞可通过减轻氧化应激、改善糖尿病小鼠海马突触可塑性,提高糖尿病小鼠的认知功能。Objective To study the effect of butyphthalide(BP)on synaptic plasticity and oxidative stress in hippocampus of DM mice and the mechanism of BP in protecting their cognitive function.Methods Sixteen male db/db mice were randomly divided into DM group and BP intervention group with 8 db/m mice served as a control group.The mice in BP intervention group were treated with BP by gavage and those in DM group and control group received an equal volume of vegetable oil by gavage.Their spatial memory and learning ability were tested according to the Morris water maze escape latent period and the target quadrant free swimming time.The changes of synaptic ultrastructure in hippocampus were detected by transmission electron microscopy.The serum levels of SOD,MDA and 8-OHdG in hippocampus were measured by ELISA.The expressions of synaptophysin,NADPH oxidase subunit p67 phox and gp91 phox mRNA and protein were detected by RT-PCR and Western blot respectively.Results The 5-day escape latent period was significantly longer while the target quadrant free swimming time was significantly shorter in DM group and BP intervention group than in control group(P<0.05).The 5-day escape latent period was significantly shorter while the target quadrant free swimming time was significantly lonBP intervention group than in DM group(P<0.05).The structure of synaptic gap was significantly clearer,the number of synapses and vesicles was significantly greater,the serum level of SOD was significantly higher,the serum levels of MDA and 8-OHdG were significantly lower in hippocampal CA1 region(1.02±0.04 ng/L vs 1.35±0.11 ng/L,18.94±0.45 ng/L vs 22.19±0.34 ng/L,P<0.05).The expression levels of synaptophysin were significantly lower while those of NADPH oxidase subunit p67 phox and gp91 phox mRNA and protein were significantly lower in hippocampal CA1 region(P<0.05).Conclusion BP can improve the cognitive function of DM mice by reducing their oxidative stress and alleviating their synaptic plasticity.

关 键 词：糖尿病 海马 突触 氧化性应激 认知 

分 类 号：R28[医药卫生—中药学]