中国全科医学2017，Vol.20Issue(24)：2965-2971,7.DOI:10.3969/j.issn.1007-9572.2017.06.y32
α-硫辛酸对血糖波动状态下2型糖尿病大鼠血管内皮细胞功能及PI3K/Akt/GSK-3β通路的影响
Effects of α-lipoic Acid on the Vascular Endothelial Cell Function and PI3K/Akt/GSK-3β Pathway in Rats with Type 2 Diabetes Mellitus and High Blood Glucose Fluctuation
摘要
Abstract
Objective To explore the effects and mechanism of α-lipoic acid (α-LA) on the vascular endothelial cell function and PI3K/Akt/GSK-3β pathway in rats with type 2 diabetes mellitus (T2DM) and high blood glucose fluctuation.Methods Fifty male Sprague Dawley (SD) rats of pathogen-free were involved from July to December 2013.All the rats were fed adaptively for 2 weeks with routine diet first.Then 10 rats were chosen as normal group (NOR group) by random number table method.The other 40 rats were fed by high lipid diet for 6 weeks and then were induced by only one intraperitoneal injection of streptozotocin (STZ,35 mg/kg),then were fed with routine diet for 2 weeks.During the 10th week of intervention,fasting blood glucose (FBG) levels of rats were measured every morning by collecting blood samples from their caudal veins,meanwhile fasting blood glucose coefficient of variation (FBG-CV) were calculated.The rats,of which FBG levels higher than 16.7 mmol/L,were thought to be successful T2DM rats,and here were 36 rats.The NOR rats were induced by only one intraperitoneal injection of citric acid-trisodium citrate buffer solution after 6 weeks of intervention with routine diet,then continued to be fed with routine diet.During the 10th week of intervention,the measurement of their FBG levels was performed as the same as the other rats,and FBG-CV was calculated as well.And then the T2DM rats with higher FBG-CV value (at least 2 times of NOR group) were divided into blowing high blood glucose group (BHG group,24 rats,20 rats with higher FBG-CV were chosen for experiment),the others (NOR group<FBG-CV value≤2 times of NOR group) were steady high blood glucose group (SHG group,12 rats,10 rats with lower FBG-CV were chosen for experiment).Then BHG rats were divided into α-LA group (10 rats) and fluctuant high blood glucose control group (FHG group,10 rats) by random number table method.α-LA group was fed with high lipid diet,and intragastric administration with α-LA suspension.FHG group was fed with high lipid diet and intragastric administration with constant volume distilled water.NOR group was fed with routine diet and intragastric administration with constant volume distilled water.SHG group was fed with high lipid diet and intragastric administration with constant volume distilled water.Eight weeks later,levels of FBG,fasting insulin (FINS),markers of vascular endothelial cell damage〔hepatocyte growth factor (HGF),nitric oxide (NO)〕,oxidative stress indexes 〔superoxide dismutase (SOD) and malondialdehyde (MDA) and advanced glycation end products (AGEs)〕 were examined,expression of PI3K/Akt/GSK-3β pathway proteins (Akt,p-Akt,GSK-3β,p-GSK-3β) were measured,and markers indicating the activation degree of Akt and GSK-3β(p-Akt/Akt,p-GSK-3β/GSK-3β) were calculated.Results SHG group and FHG group had lower body weight and FINS levels but higher FBG levels than NOR group (P<0.05).α-LA group had lower body weight but higher FBG levels than NOR group (P<0.05).α-LA group had lower FBG levels but higher FINS levels than FHG group (P<0.05).SHG group and FHG group had higher HGF,NO,MDA,AGEs levels but lower SOD levels than NOR group (P<0.05).SHG group and α-LA group had lower HGF,NO,MDA,AGEs levels but higher SOD levels than FHG group (P<0.05).α-LA group had lower SOD levels but higher MDA levels than NOR group (P<0.05).SHG group and FHG group had lower p-Akt levels,p-GSK-3β levels,p-Akt/Akt,p-GSK-3β/GSK-3β than NOR group (P<0.05).α-LA group had lower p-Akt levels,p-Akt/Akt but higher GSK-3β levels,p-GSK-3β levels than NOR group (P<0.05).SHG group had higher p-Akt levels,p-Akt/Akt than FHG group (P<0.05).α-LA group had higher p-Akt levels,GSK-3β levels,p-GSK-3β levels,p-Akt/Akt,p-GSK-3β/GSK-3β than FHG group (P<0.05).Conclusion α-LA could alleviate the vascular endothelial cell damage in T2DM rats with high glucose fluctuations obviously.The protective mechanism is closely related to its effects of relieving oxidative stress and modulation of the expressions of PI3K/Akt/GSK-3β signaling pathway proteins.关键词
糖尿病,2型/硫辛酸/血糖/内皮细胞/磷酸肌醇3-激酶/蛋白激酶类/糖原合成酶激酶类Key words
Diabetes mellitus/type 2/Thioctic acid/Blood glucose/Endothelial cells/Phosphatidylinositol 3-kinase/Protein kinases/Glycogen synthase kinases分类
医药卫生引用本文复制引用
王景尚,孙明月,黄烨,殷惠军..α-硫辛酸对血糖波动状态下2型糖尿病大鼠血管内皮细胞功能及PI3K/Akt/GSK-3β通路的影响[J].中国全科医学,2017,20(24):2965-2971,7.基金项目
国家自然科学基金青年基金资助项目(81202777) （81202777）
国家自然科学基金面上项目(81573803) （81573803）
