文献类型：期刊文献

中文题名：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

英文题名：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

作者：王景尚[1];孙明月[2];黄烨[3];殷惠军[4]

第一作者：王景尚

机构：[1]首都医科大学附属北京妇产医院中医科;[2]中国中医科学院西苑医院GCP中心;[3]中国中医科学院西苑医院急诊科;[4]甘肃中医药大学中西医结合学院

第一机构：首都医科大学附属北京妇产医院中医科

年份：2017

卷号：20

期号：24

起止页码：2965

中文期刊名：中国全科医学

外文期刊名：Chinese General Practice

收录：CSTPCD;;Scopus;北大核心:【北大核心2014】；

基金：国家自然科学基金青年基金资助项目(81202777);国家自然科学基金面上项目(81573803)

语种：中文

中文关键词：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

外文关键词：Diabetes mellitus; type 2; Thioctic acid; Blood glucose; Endothelial cells; Phosphatidylinositol 3-kinase; Protein kinases; Glycogen synthase kinases

摘要：目的观察α-硫辛酸(α-LA)对血糖波动状态下2型糖尿病(T2DM)大鼠血管内皮细胞功能及磷脂酰肌醇3磷酸激酶(PI3K)/蛋白激酶B(Akt)/糖原合酶激酶3β(GSK-3β)通路的影响,初步探讨其作用机制。方法 2013年7—12月,选取50只清洁级雄性Sprague Dawley(SD)大鼠,采用普通饲料适应性喂养2周后,采用随机数字表法抽取10只作为正常组(NOR组),余下40只大鼠建造T2DM模型,给予高脂饲料6周后,一次性腹腔注射链脲佐菌素(STZ)35 mg/kg,然后给予普通饲料2周,并于第10周连续尾静脉采血检测空腹血糖(FBG),计算空腹血糖变异系数(FBG-CV),以FBG>16.7 mmol/L视为造模成功,共造模成功T2DM大鼠36只;NOR组始终给予普通饲料,并在相同时间点一次性腹腔注射等体积的柠檬酸-柠檬酸三钠缓冲液,且运用相同方法检测7次FBG,并计算FBG-CV。将造模成功的T2DM大鼠,以FBG-CV>2倍NOR组FBG-CV为波动高糖组(BHG组,24只,选取FBG-CV较大的20只进行实验),以NOR组FBG-CVObjective 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 10 th 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 T2 DM 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.