摘要
目的:观察交泰丸(Jiaotaiwan,JTW)不同配伍比例对糖尿病胰岛素抵抗、认知功能障碍的作用,并探讨其机制。方法:自发性糖尿病db/db小鼠40只,随机分为模型组,交泰丸1号组(1.68 g·kg-1),交泰丸2号组(3.36 g·kg-1),交泰丸3号组(8.40 g·kg-1),每组8只,另设同周龄C57BL/6J小鼠8只为正常组。干预8周后,检测小鼠学习记忆,空间探索能力;检测空腹血糖(fasting blood glucose,FBG),胰岛素水平(fasting insulin,Fins),计算胰岛素抵抗指数(HOMA-IR),总甘油三酯(total triglyceride,TG),总胆固醇(total cholesterol,TC),游离脂肪酸(free fatty acids,FFA),高密度脂蛋白(high density lipoprotein,HDL),低密度脂蛋白(low density lipoprotein,LDL)等;蛋白免疫印迹法(Western blot)检测tau蛋白p Ser199,p Ser202,p Ser214位点,磷酸化蛋白激酶B (p-Akt),糖原合酶激酶-3β(glycogen synthase kinase-3β,GSK-3β),磷酸化GSK-3β(p-GSK-3β)蛋白表达。结果:与模型组比较,交泰丸2,3号组FBG,Fins和HOMA-IR显著降低(P<0.01);TG,TC,HDL,FFA显著降低(P<0.01);分辨指数、穿越平台次数显著提高(P<0.01);小鼠海马tau蛋白p Ser199,p Ser202,p Ser214位点,GSK-3β蛋白表达明显降低(P<0.05,P<0.01),p-Akt,p-GSK-3β表达显著升高(P<0.01)。结论:交泰丸3号(黄连-肉桂10∶1)具有改善胰岛素抵抗及认知功能障碍的作用,可能与其抑制tau蛋白过度磷酸化,下调GSK-3β蛋白表达和上调p-Akt,p-GSK-3β表达有关。
Objective:To explore effect and mechanism of Jiaotaiwan(JTW)on cognitive impairment in diabetic mice.Method:The 40 db/db mice of spontaneous diabetes were randomly divided into model group,JTW 1 group(1.68 g·kg-1),JTW 2 group(3.36 g·kg-1),and JTW 3 group(8.40 g·kg-1),with 8 mice in each group,and 8 C57 BL/6 J mice were included into normal group.After 8 weeks of treatment,behavioral test,fasting blood glucose(FBG),fasting insulin(Fins),insulin resistance index(HOMA-IR),total triglyceride(TG),total cholesterol(TC),free fatty acids(FFA),high density lipoprotein(HDL),and low density lipoprotein(LDL)were detected.Western blot was used to detect protein expressions of p Ser199,p Ser202,pSer214,p-Akt,glycogen synthase kinase-3β(GSK-3β),phospho-GSK-3β(p-GSK-3β).Result:Compared with model group,FBG,Fins,HOMA-IR,TG,TC,HDL,FFA in JTW group decreased significantly(P<0.01),with a significant improvement in cognitive function(P<0.01),protein expressions of taupSer199,pSer202,pSer214 and GSK-3βin hippocampus of mice decreased significantly(P<0.05,P<0.01),and expressions of p-Akt and p-GSK3 beta significantly increased(P<0.01).Conclusion:JTW 3(Coptidis Rhizoma-Cinnamomi Cortex 10∶1)can alleviate insulin resistance and cognitive impairment.The mechanism may be related to the inhibition of over-phosphorylation of tau protein,the down-regulation of GSK-3βprotein expression and the up-regulation of p-Akt and p-GSK-3βexpressions.
作者
李娟娥
姜小帆
LI Juan-e;JIANG Xiao-fan;Shaanxi Provincial People’s Hospital,Third Affiliated Hospital of Xi’an Jiaotong University(Shaanxi Provincial People's Hospital,Third Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710068,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第17期23-27,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81503538)
陕西省自然科学基础研究计划项目(2018JQ8057)
