OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose <italic style="font-style: italic">via</italic> inhibiting oxidative stress

Ting Wang; Yi Yang; Yue Tian; Jin Du; Haifeng Pei; Dachun Yang

doi:10.16016/j.1000-5404.201608046

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OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose via inhibiting oxidative stress

Basic Medicin | 更新时间：2020-08-05

- OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose via inhibiting oxidative stress
- J Third Mil Med Univ Vol. 39, Issue 2, Pages: 151-156(2017)
- 作者机构：
  
  1.400038 重庆, 第三军医大学研究生管理大队
  2.610083 成都, 成都军区总医院心血管内科
- 作者简介：
- 基金信息：
  
  Supported by the National Natural Science Foundation for Young Schloars of China(81500208);the Medical Science and Technological Training Program for Youths of PLA(14QNP050);and the Supporting Project of Science and Technology Plan of Sichuan Province(2015JY0277)
- DOI：10.16016/j.1000-5404.201608046
  CLC： R322.11;R329.26;R589.2
- Published：30 January 2017，
  
  Received：8 August 2016，
  
  Accepted：17 September 2016
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Ting Wang, Yi Yang, Yue Tian, et al. OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose via inhibiting oxidative stress. [J]. J Third Mil Med Univ 39(2):151-156(2017)
DOI：

Ting Wang, Yi Yang, Yue Tian, et al. OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose via inhibiting oxidative stress. [J]. J Third Mil Med Univ 39(2):151-156(2017) DOI： 10.16016/j.1000-5404.201608046.

摘要

目的

研究高糖高脂对心肌细胞的影响及视神经萎缩症蛋白1 (optical atrophy-1

OPA1) 在其中的具体作用。

方法

将高糖培养基培养的小鼠心肌细胞分为3组：高糖+0、200、400 μmol/L软脂酸钠组

并分别干预8 h和16 h。采用siRNA敲低心肌OPA1表达，进一步将400 μmol/L 软脂酸钠组分为对照组、OPA1 siRNA干预组、Scra siRNA干预组、OPA1 siRNA+NAC干预组。通过流式细胞仪检测各组心肌细胞在不同时间点的凋亡水平，q-PCR法检测心肌细胞中OPA1 mRNA的表达情况，DHE染色法与ELISA试剂盒测定心肌细胞中活性氧簇 (reactive oxygen species

ROS) 水平。

结果

心肌细胞凋亡水平随着软脂酸钠的浓度和干预时间逐渐增加 (

＜0.05)。与对照组相比，高脂干预明显抑制心肌细胞中OPA1的表达，同时显著地促进ROS生成(

＜0.05)。通过OPA1 siRNA干扰OPA1的表达水平后，高脂诱导的心肌细胞凋亡与ROS生成进一步增加(

＜0.05)；相反地，抗氧化剂N-乙酰半胱氨酸(N-acetyl-L-cysteine

NAC)逆转了上述OPA1抑制所导致的心肌细胞凋亡。

结论

高脂血症会进一步增加糖尿病心肌细胞的易损性，OPA1可以通过抑制氧化应激反应促进伴有高脂血症糖尿病条件下的心肌细胞存活。

Abstract

Objective

To investigate the effect of high fat and high glucose on cardiomyocytes and explore the role of optical atrophy-1 (OPA1) in the process.

Methods

Cardiomyocytes cultured with high-glucose medium underwent sodium palmitate intervention for 8 and 16 h

and were divided into 3 groups: high glucose+ 0 μmol/L sodium palmitate group

high glucose+200 μmol/L sodium palmitate group

and high glucose+400 μmol/L sodium palmitate group. Then

high glucose+400 μmol/L sodium palmitate group was further divided into 4 subgroups: control subgroup

OPA1 siRNA subgroup

Scra siRNA subgroup

and OPA1 siRNA+N-acetyl-L-cysteine (NAC) subgroup. The apoptosis of cardiomyocytes was measured by flow cytometry at given time points. The mRNA expression of OPA1 was determined by q-PCR

and the levels of reactive oxygen species (ROS) were detected by DHE staining and ELISA.

Results

The apoptotic ratio of cardiomyocytes was gradually increased in a dose- and time-dependent manner (

＜0.05). Moreover

compared with the control subgroup

high fat obviously inhibited the expression of OPA1 in the cardiomyocytes and significantly aggravated the generation of ROS (

＜0.05). Most importantly

the knockdown of OPA1 further aggravated the cardiomyocyte apoptosis and the level of ROS induced by high fat (

＜0.05). In contrast

these effects mentioned above were reversed by the application of antioxidant NAC (

＜0.05).

Conclusion

Hyperlipidmia increases the vulnerability of diabetic cardiomyocytes

and OPA1 can improve cardiomyocyte survival in diabetic hyperlipidmia

via

inhibiting oxidative stress.

关键词

糖尿病高脂心肌细胞视神经萎缩症蛋白1氧化应激

Keywords

diabeteshigh fatcardiomyocytesoptical atrophy-1oxidative stress

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⁰

OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose via inhibiting oxidative stress

DOI：10.16016/j.1000-5404.201608046

摘要

Abstract

关键词

Keywords

references