醒脑益智剂联合罗格列酮改善2型糖尿病小鼠记忆障碍的作用机制  

Effects of Xingnao Yizhi Prescription with Rosiglitazone on Type 2 Diabetic Cognitive Impairment in Mice and Its Action Mechanisms

作　　者：毛黎黎 高晓斐 岳仁宋[4] MAO Lili;GAO Xiaofei;YUE Rensong(Traditional Chinese Medicine of Chengdu University;Traditional Chinese Medicine of Sichuan Provincial Academ;Traditional Chinese Medicine Hospital of Chongqing,Affiliated Traditional Chinese Medicine Hospital of Chengdu University,Chengdu 610072,Chin)

机构地区：[1]成都中医药大学临床医学院,四川成都610072 [2]四川省中医药科学院,四川成都610042 [3]重庆市中医院,重庆400010 [4]成都中医药大学附属医院,四川成都610072

出　　处：《中国民族民间医药》2018年第11期14-18,共5页Chinese Journal of Ethnomedicine and Ethnopharmacy

摘　　要：目的:研究醒脑益智剂联合罗格列酮对2型胰岛素抵抗型糖尿病痴呆小鼠学习记忆能力及胰岛素信号通路的影响及其作用机制。方法:雄性10周龄C57BL小鼠16只为正常对照组,雄性10周龄KKay小鼠80只为模型组,高糖高脂饲料喂养8周后,随机血糖≥13.9mmol/L为模型成立,随机分为模型对照组、阳性对照组和联合给药高、中、低剂量组。阳性组每日用马来酸罗格列酮片(0.003g/kg)灌胃,联合给药高、中、低剂量组每日分别用马来酸罗格列酮片(0.003g/kg)和醒脑益智剂(3.6、7.2、14.4g/kg)灌胃,对照组每日用等体积生理盐水ig,连续42 d。给药前后分别行1次Morris水迷宫实验,最后1次水迷宫后立即在冰具上采集样本,检测小鼠大脑皮层及海马中PI-3K/Akt的蛋白表达水平以及GSK-3β(糖原合酶激酶-3β)、Tau蛋白及P-Tau(Tau蛋白磷酸化)水平。结果:与正常组相比,模型组小鼠的平台潜伏期明显偏高(P<0.05),PI-3K活性明显偏低(P<0.05),GSK-3β和p-Tau水平均明显偏高(P<0.05),联合给药组各项指标与正常组无明显差异。与模型组相比,阳性组与之各项指标差异均不明显,联合给药组平台潜伏期均明显偏低(P<0.05),PI-3K/Akt活性均明显偏高(P<0.05),GSK-3β和P-Tau水平均明显偏低(P<0.05),其中以联合给药中剂量组效果最为明显。给药后各组间InsR水平差异不大。结论:在常规改善胰岛素抵抗的基础上,醒脑益智剂能有效提高2型糖尿病痴呆小鼠学习、记忆能力,其可能的作用机制为改善大脑海马胰岛素信号传导通路,增强PI-3K活性,降低GSK-3β表达和Tau蛋白磷酸化水平。Objective To study the effect and mechanism of Xingnao Yizhi prescription with Rosiglitazone on memory impairment of type 2 diabetes. Method Sixteen 10-week C57 BL mice were as normal group and 80 Kkay mice 10-week with high blood sugar（ ≥13. 9 mmol/L） as model group,positive group and composite group with high,middle and low doses. Fed the positive group was given rosiglitazone maleate tablets（ 0. 003 g/kg）,and composite group was given rosiglitazone maleate tablets（ 0. 003 g/kg） and Xingnao Yizhi prescription（ 3. 6、7. 2、14. 4 g/kg）. Normal and model groups were given equal volume of saline. After two Morris water mazes,samples were collected and immunohistochemical method was used to test 1-phosphatidylinosital 3-kinase（ PI-3K）/Akt and western blotting was used to test glycogen synthase kinase-3,Tau protein and phosphorylation of Tau protein. Result Compared with normal group,model group used much longer time to find the plat（ P〈0. 05）,had less active PI-3K（ P 0. 05） and more active GSK-3β and p-Tau,no significant differences in the composite group and normal group. Compared with control group,there was no significant differences in positive group,while PI-3K/Akt,GSK-3β and P-Tau were contrary in composite group（ P 0. 05）. Conclusion Xingnao Yizhi prescription can improve the study and memory level of type 2 diabetes mice with cognitive impairment based on the reducing of plasma insulin,and the possible mechanism may enhance the activity of PI-3K,and reduce the level of GSK-3β,P-Tau.

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：R965[医药卫生—药理学]