达格列净对糖尿病大鼠血管内皮功能及PTEN/PI3K/Akt信号通路的影响  

Effects of dapagliflozin on vascular endothelial function and PTEN/PI3K/Akt signaling pathway in diabetic rats

作　　者：史丽[1] 胡婷婷[2] 李红 张三明[2] 刘智慧 左惠玲 胡利梅[1] 任卫东[1] Li Shi;Ting-ting Hu;Hong Li;San-ming Zhang;Zhi-hui Liu;Hui-ling Zuo;Li-mei Hu;Wei-dong Ren(Department of Endocrinology,The First Affiliated Hospital of Hebei North University,Shijiazhuang,Hebei 075000,China;International Medical Services,The First Affiliated Hospital of Hebei North University,Shijiazhuang,Hebei 075000,China;Zhangjiakou Municipal Health Commission,Zhangjiakou,Hebei 075000,China;Department of Nuclear Medicine,The First Affiliated Hospital of Hebei North University,Shijiazhuang,Hebei 075061,China)

机构地区：[1]河北北方学院附属第一医院内分泌科,河北张家口075000 [2]河北北方学院附属第一医院国际医疗部,河北张家口075000 [3]张家口市卫生健康项目管理中心,河北张家口075000 [4]河北北方学院附属第一医院核医学科,河北张家口075000

出　　处：《中国现代医学杂志》2022年第10期13-17,共5页China Journal of Modern Medicine

基　　金：2021年度河北省“三三三人才工程”资助项目(No:A202103006);张家口市科技攻关计划项目(No:2021040D)。

摘　　要：目的探究达格列净对糖尿病大鼠血管内皮功能及PTEN/PI3K/Akt信号通路的影响。方法将30只SPF级SD雄性大鼠随机分为对照组、模型组、达格列净组,各10只。模型组、达格列净组成功复制糖尿病模型后,达格列净组给予1 mg/(kg·d)达格列净灌胃处理,连续4周;模型组、对照组分别同时间灌胃等量柠檬酸-柠檬酸钠缓冲溶液。采用酶联免疫吸附试验检测血清内皮素1(ET-1)、缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)水平;苏木精-伊红染色观察大鼠主动脉血管组织病理学变化;Western blotting检测大鼠血管内皮组织PTEN/PI3K/Akt信号通路蛋白的表达。结果达格列净组大鼠一般情况好于模型组。达格列净组大鼠主动脉病理变化较模型组改善。与对照组比较,模型组、达格列净组大鼠血清ET-1、HIF-1α、VEGF水平升高(P<0.05),但达格列净组大鼠血清ET-1、HIF-1α、VEGF水平低于模型组(P<0.05)。与对照组比较,模型组、达格列净组大鼠血管内皮组织PTEN蛋白相对表达量降低(P<0.05),p-PI3K/PI3K、p-Akt/Akt蛋白相对表达量升高(P<0.05);但达格列净组较模型组大鼠血管内皮组织PTEN蛋白相对表达量升高(P<0.05),p-PI3K/PI3K、p-Akt/Akt蛋白相对表达量降低(P<0.05)。结论达格列净可能通过促进PTEN/PI3K/Akt信号通路活化,改善糖尿病大鼠血管内皮功能损伤,从而防治糖尿病及其并发症的发生。Abstarct:Objective To explore the effects of dapagliflozin on vascular endothelial function and PTEN/PI3 K/Akt signaling pathway in diabetic rats.Methods A total of 30 SPF male SD rats were randomly divided into control group,model group and dapagliflozin group,each group with 10 rats.The diabetic models were successfully established in the model group and the dapagliflozin group,and the rats in dapagliflozin group were given 1 mg/(kg·d)of dapagliflozin by gavage for 4 weeks.The rats in the model group and the control group were given an equal volume of sodium citrate buffer solution by gavage at the same time.Serum levels of endothelin-1(ET-1),hypoxiainducible factor(HIF)-1αand vascular endothelial growth factor(VEGF)were detected by enzyme-linked immunosorbent assay.Hematoxylin and eosin staining was used to observe the histopathological changes of rat aortas.The expressions of proteins associated with the PTEN/PI3 K/Akt pathway in rat aortas were detected by Western blotting.Results The overall conditions of the rats in the dapagliflozin group were greater than those in the model group,and the pathologies of rat aortas were ameliorated in the dapagliflozin group compared with the model group.The serum levels of ET-1,HIF-1αand VEGF in the model group and the dapagliflozin group were higher than those in the control group(P<0.05),while they were lower in the dapagliflozin group relative to those in the model group(P<0.05).Compared with the control group,the relative protein expression of PTEN was lower,but the relative protein expressions of p-PI3 K/PI3 K and p-Akt/Akt were higher in the model group and the dapagliflozin group(P<0.05).Besides,the relative protein expression of PTEN in the dapagliflozin group was higher than that in the model group,while the relative protein expressions of p-PI3 K/PI3 K and p-Akt/Akt in the dapagliflozin group were lower than those in the model group(P<0.05).Conclusions Dapagliflozin may enhance the activation of PTEN/PI3 K/Akt pathway and mitigate the vascular endothelial dys

关 键 词：糖尿病 达格列净 血管内皮功能 PTEN/PI3K/Akt信号通路 大鼠 

分 类 号：R587.1[医药卫生—内分泌]