康黎, 邹勇, 李宏增, 刘军, 张莹. 二十碳五烯酸在糖尿病心肌病损伤中的作用及机制[J]. 心脏杂志, 2019, 31(5): 521-525. DOI: 10.12125/j.chj.201901048
    引用本文: 康黎, 邹勇, 李宏增, 刘军, 张莹. 二十碳五烯酸在糖尿病心肌病损伤中的作用及机制[J]. 心脏杂志, 2019, 31(5): 521-525. DOI: 10.12125/j.chj.201901048
    li KANG, Yong ZOU, Hong-Zeng LI, Jun LIU, Ying ZHANG. Role and mechanism of eicosapentaenoic acid in cardiac injury of diabetic cardiomyopathy[J]. Chinese Heart Journal, 2019, 31(5): 521-525. DOI: 10.12125/j.chj.201901048
    Citation: li KANG, Yong ZOU, Hong-Zeng LI, Jun LIU, Ying ZHANG. Role and mechanism of eicosapentaenoic acid in cardiac injury of diabetic cardiomyopathy[J]. Chinese Heart Journal, 2019, 31(5): 521-525. DOI: 10.12125/j.chj.201901048

    二十碳五烯酸在糖尿病心肌病损伤中的作用及机制

    Role and mechanism of eicosapentaenoic acid in cardiac injury of diabetic cardiomyopathy

    • 摘要:
        目的  探讨二十碳五烯酸(eicosapentaenoic acid,EPA)对糖尿病心肌病损伤的作用及其机制。
        方法  小鼠随机分为正常 (Con) 组、EPA处理 (Con+EPA) 组、糖尿病模型 (DM) 组、糖尿病模型EPA处理 (DM+EPA) 组。腹腔注射链脲佐菌素(streptozotocin, STZ)构建糖尿病小鼠模型,超声检测各组小鼠心脏功能,麦胚凝集素 (wheat germ agglutinin, WGA)检测心肌细胞横截面积,TUNEL化学染色检测细胞凋亡率,Western blot检测小鼠心脏组织cleaved caspase-3、Bax、Bcl-2、动力相关蛋白(dynamin-related protein, Drp)1和磷酸化腺苷酸活化蛋白激酶(phospho-AMP-activated protein kinase, P-AMPK)的表达水平。
        结果  与Con组相比,DM组小鼠左心室收缩末内径(left ventricular end-systolic diameter, LVESD)和左心室舒张末内径(left ventricular end diastolic diameter, LVEDD)值上调,左室射血分数(left ventricular ejection fraction,LVEF)和左室短轴缩短率(left Ventricular Fraction shortening, LVFS)下降,细胞横截面积增大,凋亡率显著增加,凋亡相关蛋白cleaved caspase-3、Bax表达增加、Bcl-2表达降低,同时p-AMPK/AMPK比值升高,Drp1表达增多(P < 0.05)。但是EPA处理DM小鼠可使LVESD、LVEDD值下调,LVEF、LVFS值上升,心肌横截面积减小,凋亡率降低,并使cleaved caspase-3、Bax表达降低、Bcl-2表达增加(P < 0.05)。而且EPA处理DM小鼠后AMPK磷酸化进一步增加,Drp1表达减少。
        结论  EPA通过抑制心肌肥大及凋亡改善糖尿病诱导的心功能损伤,其机制可能与AMPK/Drp1信号相关。

       

      Abstract:
        AIM  To investigate the effects and mechanism of eicosapentaenoic acid (EPA) on cardiac functions in diabetic mice.
        METHODS  The mice were randomly divided into four groups: wild type mice group (Con), EPA intervention group (Con+EPA), diabetic group (DM), and diabetes EPA intervention group (DM+EPA). Diabetes was induced by intraperitoneal injections of STZ. The cardiac geometry and functions were assessed using transthoracic echocardiography. Wheat germ agglutinin (WGA) staining and TUNEL staining were performed to reveal the extent of myocyte hypertrophy and apoptosis. Expressions of cleaved caspase-3, Bax, Bcl-2, Dynamin-related protein 1(Drp1) and Phospho-AMP-activated protein kinase (p-AMPK) were detected using Western blot.
        RESULTS  The mice in DM group showed increase of left ventricular end-systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD), reduction of left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), increase of myocyte cross-sectional area and elevated apoptosis index, compared with those in Con group(P < 0.05). Western blot analysis also revealed accumulation of cleaved caspase-3, Bax and reduction of Bcl-2 in DM group compared with those in Con group. In addition, elevated p-AMPK/AMPK ratio and Drp1 expression were found in DM group compared with those in Con group(P < 0.05). However, the administration of EPA significantly increased LVEF and LVFS, decreased LVESD, LVEDD, myocardial cross-sectional area and apoptosis index in DM mice(P < 0.05). The administration of EPA in DM mice decreased cleaved caspase-3 and Bax expression, increased Bcl-2expression, improved p-AMPK/ AMPK ratio and reduced Drp1 expression(P < 0.05).
        CONCLUSION  EPA alleviates diabetes-induced cardiac dysfunction by inhibiting myocyte hypertrophy and apoptosis and the attributed mechanism involves, at least in part, AMPK/Drp1 signaling.

       

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