中文摘要：

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-CV< FBG - CV ≤ 2 倍 NOR 组 FBG - CV 为稳定高糖组（SHG 组，12只，选取 FBG-CV较小的10只进行实验）。采用随机数字表法将 BHG 组大鼠分为α-LA组（10只）和波动高糖对照组（FHG组，10只）。 α- LA 组给予高脂饲料，灌服α- LA混悬液：FHG组给予高脂饲料，灌服等体积蒸馏水；NOR组给予普通饲料，灌服等体积蒸馏水；SHG组给予高脂饲料，灌服等体积蒸馏水。干预8周后，检测各组大鼠FBG、空腹血浆胰岛素(FINS）水平，血管内皮细胞损伤指标〔 肝细胞生长因子（HGF）、一氧化氮（NO）〕、氧化应激指标〔超氧化物歧化酶（ SoD ）、丙二醛（ MDA ）、糖基化终末产物（ AGEs ） 〕 水平， PI3K/Akt/GSK -3β 通路蛋白 〔 Akt 、磷酸化蛋白激酶B ( p - Akt ）、 GSK - 3 β、磷酸化糖原合酶激酶 3β ( p - GSK - 3β ） 〕 水平及 Akt 、 GSK - 3 β激活程度（ p - Akt/ Akt 、 p -GS

英文摘要：

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 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 administra