恩格列净保护2型糖尿病小鼠心肌损伤机制研究  

Protective mechanism of empagliflozin against myocardial injury in mice with type 2 diabetes mellitus

作　　者：李曾一[1] 王松[1] 籍胤玺[1] 李杰玉[1] 林玉玲[1] LI Zengyi;WANG Song;JI Yinxi;LI Jieyu;LIN Yuling(Department of Endocrinology,Nanyang Central Hospital,Nanyang 473000,China)

机构地区：[1]河南南阳市中心医院内分泌科,473000

出　　处：《心肺血管病杂志》2023年第2期168-174,共7页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金(81570277)。

摘　　要：目的:基于调控转化生长因子β(TGF-β)/Smad通路和核转录因子E2相关因子2/抗氧化反应序列元件(Nrf2/ARE)信号通路分析恩格列净(EM)对2型糖尿病(DM)小鼠心肌损伤的保护作用。方法:将KK-Ay小鼠随机分为DM组和EM组(10mg·kg^(-1)·d^(-1)EM),每组30只,另取30只C57BL/6J小鼠为对照组。采用彩色多普勒测量心脏参数,半自动分析仪检测糖脂水平,分光光度计检测氧化应激指标水平,蛋白印迹法检测TGF-β/Smad通路和Nrf2/ARE信号通路相关蛋白。结果:与DM组比较,EM组心脏质量、FBG、非空腹血糖、空腹胰岛素、舒张末期室间隔厚度(IVSd)、心肌组织脂质氢过氧化物(LPO)、丙二醛(MDA)、TGF-β1(1.21±0.17)vs.(1.43±0.26)、I型胶原蛋白(CollagenⅠ)(0.93±0.18)vs.(1.71±0.23)、CollagenⅢ(1.37±0.0.21)vs.(1.96±0.34)、α-肌动蛋白(αSMA)(0.88±0.0.20)vs.(1.42±0.33)、磷酸化(p)Smad2/Smad2(0.24±0.04)vs.(0.61±0.08)及p-Smad3/Smad3(0.11±0.01)vs.(0.19±0.04)水平明显降低(P<0.05),HR、LVIDd、左心室心肌质量(LV mass)、左心室质量/体质量(LV mass/BW)、LVEF、左心室短轴缩短率(FS)、左心室面积改变分数(FAC)、E波与A波峰值流速比率(E/A)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、Nrf-2(1.23±0.28)vs.(0.72±0.16)、血红素加氧酶(HO-1)(1.08±0.36)vs.(0.68±0.19)和Smad7表达(1.39±0.33)vs.(0.65±0.07)明显升高(P<0.05)。结论:EM可能通过抑制TGF-β/Smad通路、激活Nrf2/ARE通路,减缓心肌氧化应激状态,改善DM小鼠心肌功能。Objective:To explore the protective effect of empagliflozin(EM)against myocardial injury in mice with type 2 diabetes mellitus(DM)by based on transforming growth factor-β(TGF-β)/Smad pathways and nuclear transcription factor E2-related factor 2/antioxidant response element(Nrf2/ARE)signaling pathways.Methods:KK-Ay mice were randomly divided into DM group and EM group(10mg·kg^(-1)·d^(-1)EM),30 cases in each group.A total of 30 C57BL/6J mice were enrolled as control group.The cardiac parameters were measured by Color Doppler ultrasound.The glucose-lipid level was detected by semiautomatic analyzer.The levels of oxidative stress indexes were detected by spectrophotometer.The related proteins of TGF-β/Smad pathways and Nrf2/ARE signaling pathways were detected by Western blot.Results:Compared with DM group,heart weight,fasting blood glucose,non-fasting blood glucose,fasting insulin,diastolic interventricular septal depth(IVSd),lipid hydroperoxide(LPO),malondialdehyde(MDA),TGF-β1(1.21±0.17)vs.(1.43±0.26),Collagen I,(0.93±0.18)vs.(1.71±0.23),Collagen III(1.37±0.0.21)vs.(1.96±0.34),α-actin(αSMA),(0.88±0.0.20)vs.(1.42±0.33),phosphorylation(p)Smad2/Smad2(0.24±0.04)vs.(0.61±0.08)and p-Smad3/Smad3(0.11±0.01)vs.(0.19±0.04)were significantly decreased(P<0.05),while heart rate(HR),left ventricular end-diastolic diameter(LVIDd),left ventricular myocardial mass(LV mass),LV mass/body weight(LV mass/BW),EF,left ventricular fraction shortening(FS),left ventricular fractional area change(FAC),peak velocity ratio of E wave to A wave(E/A),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),Nrf-2(1.23±0.28)vs.(0.72±0.16),heme oxygenase 1(HO-1)(1.08±0.36)vs.(0.68±0.19)and Smad7(1.39±0.33)vs.(0.65±0.07)were significantly increased in EM group(P<0.05).Conclusions:EM may relieve myocardial oxidative stress and improve myocardial function in DM mice by inhibiting TGF-β/Smad pathways and activating Nrf2/ARE pathways.

关 键 词：恩格列净 转化生长因子-β/Smad通路 Nrf2/ARE信号通路 2型糖尿病 心肌损伤 

分 类 号：R54[医药卫生—心血管疾病]