丁苯酞对db/db糖尿病模型小鼠认知损害的改善作用  

L-3-n-butylphthalide Alleviates Cognitive Damage in db/db Diabetic Mice

作　　者：冀素晓 张静[1] 潘建秀 王海芳[1] 张松筠[2] JI Su-xiao;ZHANG Jing;PAN Jian-xiu;WANG Hai-fang;ZHANG Song-yun(Department of Endocrinology,Handan First Hospital,Handan 056000,China;Department of Endocrinology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]邯郸市第一医院内分泌一科,邯郸056000 [2]河北医科大学第二医院内分泌科,石家庄050000

出　　处：《中国临床神经科学》2023年第4期373-379,共7页Chinese Journal of Clinical Neurosciences

摘　　要：目的探讨丁苯酞对糖尿病认知损害及海马神经元突触可塑性的影响。方法16只健康雄性C57BL/KsJ-db/db小鼠随机分为干预组(丁苯酞120mg·kg-1·d-1,灌胃)和模型组(等量植物油,灌胃),另选取同窝出生同周龄的C57BL/KsJ-db/m小鼠作为正常组(等量植物油,灌胃),均×6周。通过Morris水迷宫实验记录逃避潜伏期及目标象限停留时间检测小鼠行为学能力,电生理学实验检测小鼠海马区长时程增强(LTP),观察神经突触可塑性变化,应用RT-PCR和Western blot法检测小鼠海马N-甲基-D-天冬氨酸受体(NMDAR)、钙/钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)和α-氨基-3-羟基-5-甲基-4-异唑-丙酸(AMPAR)的表达情况。结果与正常组比较,模型组和干预组小鼠水迷宫逃避潜伏期均延长(均P<0.05),两组的平均穿越平台次数(P<0.05)及目标象限游泳时间百分比(P<0.05)均减少;与正常组比较,模型组和干预组小鼠海马LTP明显降低(均P<0.05);正常组的海马NMDAR、CaMKⅡ及AMPAR表达水平较模型组和干预组明显增高(均P<0.05),而干预组的NMDAR、AMPAR及CaMKⅡ的表达水平明显高于模型组(P<0.05)。结论丁苯酞对糖尿病小鼠学习记忆能力有改善作用,其机制可能与上调海马NMDAR、AMPAR及CaMKⅡ的表达水平,增强LTP有关。Aim To observe efficacy of L-3-n-butyphthalide(L-NBP)on cognitive dysfunction and the synaptic plasticity in db/db mice.Methods Sixteen male C57BL/KsJ-db/db mice were randomly divided into a model group and a intervention group,and db/m mice of the same age were servered as a normal group.The animals in the intervention group were given L-NBP and those in the model group and the normal group were given vegetable oil by oral gavage.After 6 weeks of feeding,learning and memory capacity were detected by Morris water maze;electrophysiological experiment was used to record the long-term potentiation(LTP)in hippocampal CA1 area;the expressions ofα-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor(NMDAR),calcium/calmodulin-dependent protein kinase I(CaMK I)and AMPAR mRNA and protein were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot in the hippocampus.ResultssCompared with the normal group[(22.71±4.38)s,(7.00±0.93)n/min,(54.67±2.32)%],escape latency was prolonged in the model group and intervention group[(54.22±3.14)s,(32.49±5.48)s,P<0.05],significantly longer than the normal group[(22.71±4.38)s,P<0.05].Moreover,the number of target crossings in 90 s[(2.88±0.99)n/min,(4.38±0.92)n/min,P<0.05]and the percentage of swimming time of the target quadrant in the target quadrant[(27.68±3.89)%,(48.49±3.58)%,P<0.05]were decreasing in the two groups,significantly less than those in the normal group[(7.00±0.93)n/min,(54.67±2.32)%,P<0.05j.L-NBP significantly improved learning and memory capability in the intervention group.In the electrophysiological experiments,population spike(PS)amplitude significantly decreased in the model group and intervention group than that in the normal group[(250.97±8.45)%vs.(132.32±2.44)%,(170.21±4.19)%,P<0.05].L-NBP treatment restored PS amplitude,and also significantly increased the expression of NMDAR,CaMKI and AMPAR in the hippocampus of diabetic mice(P<0.05).Conclusion L-NBP can improve the cognitive function of diabetes mice by up-reg

关 键 词：糖尿病 认知损害 丁苯酞 长时程增强 海马 N-甲基-D-天冬氨酸受体 钙/钙调素依赖性蛋白激酶Ⅱ α-氨基-3-羟基-5-甲基-4-异唑-丙酸 

分 类 号：R587.1[医药卫生—内分泌] R749.2[医药卫生—内科学]