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Nrf2/Sirt3信号通路在Irisin抵抗糖尿病心肌损伤中的作用

熊祥 卢林鹤 马继鹏 邵亚兰 李兰兰 金屏 刘洋 刘金成 杨剑 柏本健

熊祥, 卢林鹤, 马继鹏, 邵亚兰, 李兰兰, 金屏, 刘洋, 刘金成, 杨剑, 柏本健. Nrf2/Sirt3信号通路在Irisin抵抗糖尿病心肌损伤中的作用[J]. 心脏杂志, 2023, 35(1): 1-8. doi: 10.12125/j.chj.202205002
引用本文: 熊祥, 卢林鹤, 马继鹏, 邵亚兰, 李兰兰, 金屏, 刘洋, 刘金成, 杨剑, 柏本健. Nrf2/Sirt3信号通路在Irisin抵抗糖尿病心肌损伤中的作用[J]. 心脏杂志, 2023, 35(1): 1-8. doi: 10.12125/j.chj.202205002
Xiang XIONG, Lin-he LU, Ji-peng MA, Ya-lan SHAO, Lan-lan LI, Ping JIN, Yang LIU, Jin-cheng LIU, Jian YANG, Ben-jian BAI. Protective role of irisin against diabetic cardiomyopathy via Nrf2/Sirt3 signaling pathway[J]. Chinese Heart Journal, 2023, 35(1): 1-8. doi: 10.12125/j.chj.202205002
Citation: Xiang XIONG, Lin-he LU, Ji-peng MA, Ya-lan SHAO, Lan-lan LI, Ping JIN, Yang LIU, Jin-cheng LIU, Jian YANG, Ben-jian BAI. Protective role of irisin against diabetic cardiomyopathy via Nrf2/Sirt3 signaling pathway[J]. Chinese Heart Journal, 2023, 35(1): 1-8. doi: 10.12125/j.chj.202205002

Nrf2/Sirt3信号通路在Irisin抵抗糖尿病心肌损伤中的作用

doi: 10.12125/j.chj.202205002
基金项目: 国家自然科学基金项目(81870216,82070264,82070503,82000373)
详细信息
    作者简介:

    熊祥,硕士生 Email:xiongxiangdoctor@hotmail.com

    通讯作者:

    柏本健,主任医师,主要从事心脏疾病临床研究 Email:baibenjian1212@163.com

  • 中图分类号: R285.5;R587.2

Protective role of irisin against diabetic cardiomyopathy via Nrf2/Sirt3 signaling pathway

  • 摘要:   目的  明确鸢尾素(Irisin)在糖尿病心肌损伤中的作用及机制。  方法  将小鼠以随机数字表法分为4组:NS组、Irisin组、糖尿病心肌病(DCM)组、DCM-Irisin干预组;体外实验分组:高糖高脂组(HG/HF)、HG/HF-Irisin干预组、HG/HF-Irisin干预-Nrf2抑制剂组、HG/HF-Nrf2抑制剂组、HG/HF-Nrf2激动剂组、HG/HF-Nrf2激动剂-Sirt3抑制剂组、HG/HF- Irisin干预-Sirt3抑制剂组。采用Western blot、RT-PCR检测自噬及凋亡相关分子表达、CCK-8检测细胞活力、MMP和ATP检测评估线粒体功能、TUNEL染色检测细胞凋亡。  结果  糖尿病小鼠心肌组织及高糖高脂诱导的H9c2细胞中Irisin的蛋白及mRNA表达量显著降低(P<0.05),而LC3II/I和Cleaved caspase 3的表达量显著增加(P<0.01),同时可见Nrf2及P62的蛋白表达量显著降低(P<0.01)。Irisin处理后,可部分缓解DCM导致的心肌细胞损伤。在给予Nrf2抑制剂ML385后,Irisin的保护作用被部分抵消,同时观察到Sirt3蛋白表达被显著抑制(P<0.01)。而在高糖高脂条件下,抑制Sirt3活性则可消除因上调Nrf2对H9c2细胞的有益作用。  结论  Irisin通过激活Nrf2/Sirt3信号通路减轻糖尿病心肌病诱导的心肌细胞损伤。

     

  • 图  1  糖尿病小鼠和HG/HF诱导细胞中Irisin及Insulin的变化

    n=3。与NS组比较,aP<0.05,bP<0.01;与PBS组比较,cP<0.05,dP<0.01

    图  2  Irisin对糖尿病小鼠中自噬性细胞死亡相关蛋白的影响

    1:NS组;2:Irisin组;3:DCM组;4:DCM-Irisin组。n=3。与NS组比较,aP<0.05,bP<0.01;与DCM组比较,cP<0.05

    图  3  Irisin对高糖高脂处理的H9c2细胞中自噬性细胞死亡相关蛋白的影响

    1:PBS组;2:Irisin组;3:HG/HF组;4:HG/HF-Irisin组。n=3。与PBS组比较,bP<0.01;与HG/HF组比较,cP<0.05

    图  4  Irisin和ML385对HG/HF诱导细胞中自噬性细胞死亡相关蛋白、细胞活力以及血清LDH的影响

    1:HG/HF组;2:HG/HF-Irisin组;3:HG/HF-Irisin-ML385组;4:HG/HF-ML385组。n=3。与HG/HF组比较,aP<0.05,bP<0.01;与HG/HF-Irisin组比较,cP<0.05,dP<0.01 ;与PBS组比较,fP<0.01

    图  5  Irisin和ML385对HG/HF诱导细胞中MMP及ATP含量的影响

    1:HG/HF组;2:HG/HF-Irisin组;3:HG/HF-Irisin-ML385组;4:HG/HF-ML385组。n=3。与HG/HF组比较,aP<0.05,bP<0.01;与HG/HF-Irisin组比较,cP<0.05

    图  6  Oltipraz和3-TYP对HG/HF诱导的细胞中自噬性细胞死亡相关蛋白及ATP含量的影响

    1:HG/HF组;2:HG/HF-Oltipraz组;3:HG/HF-Oltipraz-3-TYP组。n=3。与HG/HF组比较,aP<0.05,bP<0.01;与HG/HF-Oltipraz组比较,cP<0.05,dP<0.01

    图  7  Oltipraz和3-TYP对HG/HF诱导细胞凋亡及血清LDH的影响

    1:HG/HF组;2:HG/HF-Oltipraz组;3:HG/HF-Oltipraz-3-TYP组。n=3。与HG/HF组比较,aP<0.05,bP<0.01;与HG/HF-Oltipraz组比较,cP<0.05

    图  8  Irisin和3-TYP对HG/HF诱导的细胞中自噬性细胞死亡相关蛋白的影响

    1:HG/HF组;2:HG/HF-Irisin组;3:HG/HF-Irisin-3-TYP组。n=3.。与HG/HF组比较,aP<0.05,bP<0.01;与HG/HF-Irisin组比较,cP<0.05,dP<0.01

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  • 收稿日期:  2022-05-01
  • 修回日期:  2022-07-13
  • 刊出日期:  2023-02-25

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