醒脑益智剂对2型糖尿病轻度认知功能障碍小鼠的影响及机制研究  

Effects of Xingnao Yizhi Prescription on type 2 diabetic cognitive impairment in mice and its action mechanisms

作　　者：高晓斐[1] 张静[1] 毛黎黎 朱侣 岳仁宋[2] 

机构地区：[1]成都中医药大学临床医学院,成都医学博士610072 [2]成都中医药大学附属医院内分泌科,成都610072

出　　处：《医学研究生学报》2016年第8期796-800,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81072775);四川省科技计划项目(2015SZ0100)

摘　　要：目的现代研究发现,2型糖尿病患者更容易发展成认知功能障碍。文中研究醒脑益智剂对2型糖尿病轻度认知功能障碍小鼠学习、记忆能力及胰岛素信号传导通路的影响及机制。方法 12只雄性10周龄C57BL小鼠为正常组,60只雄性10周龄KK-Ay小鼠高糖高脂饲料喂养8周后,检测随机血糖≥16.7 mmol/L后随机数字表法分为模型组、罗格列酮组、醒脑益智剂高、中、低剂量组。罗格列酮组每日用马来酸罗格列酮片(0.003 g/kg)灌胃给药,醒脑益智剂低、中、高剂量组每日用醒脑益智剂生药(3.6、7.2和14.4 g/kg)及马来酸罗格列酮片(0.003 g/kg)灌胃给药,正常组和模型组每日用等体积等渗盐水灌胃给药,给药6周。分别于给药前后各行1次Morris水迷宫动物行为学实验,记录平台潜伏期结果并做比较。水迷宫后及时于冰台上制备样本。采用免疫组化检测各组小鼠大脑海马中磷脂酰肌醇-3激酶(PI-3K)的蛋白表达水平;Western blot检测糖原合酶激酶-3β(GSK-3β)、胰岛素受体(Ins R)水平、Tau蛋白及Tau蛋白磷酸化(P-Tau)水平。结果与平台潜伏期第1天比较,除模型组外,其他各组第5天平台潜伏期均缩短,差异有统计学意义(P<0.05);与模型组第5天平台潜伏期[(76±21)s]比较,正常组[(58±25)s]、罗格列酮组[(68±33)s]、醒脑益智剂低剂量组[(56±24)s]、醒脑益智剂中剂量组[(51±18)s]、醒脑益智剂高剂量组[(59±20)s]均缩短(P<0.05);正常组和醒脑益智剂低、中、高剂量组平台象限概率均增加(P<0.05)。与模型组比较,正常组和醒脑益智剂低、中、高剂量组平台象限概率均增加(P<0.05)。与罗格列酮组比较,醒脑益智剂中剂量组第5天平台潜伏期缩短(P<0.05),醒脑益智剂低、中、高剂量组平台象限概率增加(P<0.05)。各组小鼠大脑海马中Ins R水平及Tau蛋白总量差异无统计学意义(P>0.05)。与模型组相比,醒脑益智剂各组在Ser396位点上的Tau蛋白�Objective Modem studies show that patients with type 2 diabetes mellitus （DM） are more likely to develop cog- nitive impairment than normal elderly people, and the cognitive problems caused by this problem call for immediate solution. The pur- pose of this study was to explore the effects of Xingnao Yizhi Prescription （XYP） on learning, memory, and insulin signaling in mice with type 2 DM cognitive impairment. Methods Twelve 10-week-old C57BL male mice were used as normal controls and another 60 age-matched KK-Ay male mice were fed with high-fat and -sugar diet for 8 weeks till blood sugar was ≥ 16.7 mmol/L. Then the model mice were divided into five groups of equal number： model control, rosiglitazone （0.003 g/kg）, high-dose XYP （14.4 g/kg）, medi- um-dose XYP （7.2 g/kg）, and low-dose XYP （3.6 g/kg）, fed intragastically once daily, while the normal and model controls were given normal saline, all for 6 weeks. Animal behavioral tests with Morris Water Maze were performed before and after medication, fol- lowed by timely specimen preparation in the ice stage. The protein expression of PI-3K in the hippocampus of the mice was detected by immunohistochemistry and the levels of GSK-313, insulin receptor （Ins R）, Tan protein and Tau protein phosphorylation （P-Tau） were determined by Western blot. Results Compared with the normal control mice, the model controls showed significantly longer time to find the plat （58 ± 25 vs 76 ± 21, P 〈 0.05）, lower PI-3K/Akt activity （99 vs 15, P 〈 0.05）, and higher levels of GSK-3β （0.248 vs 1. 001, P 〈 0.05 ） and p-Tau （0.116 vs 0. 672, P 〈 0.05）, but with no statistically significant differences from the those of the rosiglitazone group. In comparison with the model controls, the mice in the high-, medium-, and low-dose XYP groups exhibited remarkably shorter time to find the plat （76-± 21 vs 56 ± 24, 51 ± 18, and 59 ± 20, P 〈 0.05）, higher PI-3K/Akt activity （ 15 vs 90, 93, and 87, P 〈 0.05）, and lower le

关 键 词：醒脑益智剂 糖尿病性记忆障碍 GSK-3Β TAU蛋白 PI-3K 

分 类 号：R749[医药卫生—神经病学与精神病学]