丁苯酞对糖尿病小鼠学习记忆及海马长时程增强的作用及机制  

Effect of Dl-3-n-butyphthalid on learning and memory deficiency and hippocampus synaptic long term potentiation in diabetic mice

作　　者：高明[1] 白笑梅 冀素晓 郝慧瑶[1] 张松筠[1] Gao Ming;Bai Xiaomei;Ji Suxiao;Hao Huiyao;Zhang Songyun(Department of Encrinology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China;Department of Encrinology,Hangang Hospital,Handan 056001,China;Department of Encrinology,Handan First Hospital,Handan 056000,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]邯钢医院消化内分泌一科,邯郸056001 [3]邯郸市第一医院内分泌科,056000

出　　处：《中华行为医学与脑科学杂志》2019年第7期617-621,共5页Chinese Journal of Behavioral Medicine and Brain Science

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

摘　　要：目的探讨丁苯酞对2型糖尿病db/db小鼠记忆学习功能的作用并探讨其内在机制。方法16只雄性db/db小鼠随机分为丁苯酞组和糖尿病组,每组8只,另取8只雄性同龄的db/m小鼠作为对照组。丁苯酞组给予丁苯酞灌胃治疗,糖尿病组和对照组给予等体积植物油灌胃,6周后应用Morris水迷宫检测小鼠的空间记忆和学习能力,电生理技术检测小鼠海马区长时程增强(LTP)的变化,实时定量PCR和Western免疫印迹法检测海马区VEGF、caspase-3、Aβ1-42的mRNA和蛋白表达。结果与正常对照组[(21.49±4.41)s,(7.00±0.60)次]相比,糖尿病组和丁苯酞组小鼠的第5天逃避潜伏期均延长[(51.69±5.45) s、(26.92±4.76)s ,t=9.21,2.35;均P<0.05 ],穿越平台次数减少[(2.34±0.27)次、(4.95±0.54)次,t=-6.56,-2.49;均P<0.05 ]。与对照组比较,糖尿病组小鼠和丁苯酞组小鼠海马区LTP水平显著下降[(255.90±54.24)%、(130.97±14.08 )%、(176.17±18.96)%,t=-4.25,-2.38;均P<0.05 ],VEGF、caspase-3、Aβ1-42表达升高,差异均有统计学意义(t=4.59,8.42;7.36,3.85;3.84,2.11;均P<0.05)。与糖尿病组比较,丁苯酞组第5天逃避潜伏期显著缩短,跨越平台次数和海马区LTP显著增加(t=-7.25,4.06,3.25;均P<0.05),caspase-3、Aβ1-42表达显著减少,VEGF表达显著增加(t=-4.14,-2.31,3.42;均P<0.05)。结论丁苯酞可能通过抑制糖尿病小鼠海马区Aβ1-42沉积,上调VEGF表达,抑制凋亡,促进LTP,改善糖尿病小鼠的认知功能。Objective To study the effect and mechanism of Dl-3-n-butylphthalide(NBP) on memory and learning ability in type 2 diabetes model db/db mice. Methods Sixteen male db/db mice were randomly divided into the NBP group and diabetes group, with 8 mice in each group.Eight male db/m mice of the same age were treated as the control group. NBP group was given NBP by gavage, while diabetes group and control group were given equal volume vegetable oil by gavage. After 6 weeks treatment, Morris water maze was used to examine the spatial memory and learning ability of the mice in each group. The changes of long-term potentiation (LTP) in the hippocampus area of mice were detected by electrophysiological techniques. RT-PCR and Western blot were employed to measure expressions of VEGF, caspase-3, and Aβ1-42 in hippocampus of mice. Results Compared with the control group((21.49±4.41)s), average escape latency of day 5 in the diabetes group and NBP group were increased significantly ((51.69±5.45)s,(26.92±4.76)s, t=9.21, 2.35, both P<0.05). Compared with the control group(7.00±0.60), the number of crossing the target platform in the diabetes group and NBP group were decreased significantly(2.34±0.27),(4.95±0.54), t=-6.56,-2.49;both P<0.05). Compared with the control group((255.90±54.24)%), LTP level in hippocampus of the diabetes group and NBP group were significantly decreased(130.97±14.08)%,(176.17±18.96)%, t=-4.25,-2.38;both P<0.05). The relative expression of VEGF, caspase-3, and Aβ1-42 in the diabetes group and NBP group were significantly increased compared with those of the control group (t=4.59, 8.42;7.36, 3.85;3.84, 2.11;all P<0.05). Compared with the diabetes group, the escape latency of day 5, the number of crossing the target platform and LTP level were improved in the NBP group (t=-7.25, 4.06, 3.25;all P<0.05). The decreased expression of caspase-3, Aβ1-42 and increased expression of VEGF were reversed after NBP treatment in db/db mice (t=-4.14,-2.31, 3.42;all P<0.05). Conclusion NBP might improve cognitiv

关 键 词：2型糖尿病 认知功能 丁苯酞 血管内皮生长因子 AΒ1-42 小鼠 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学] R-332[医药卫生—临床医学]