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视神经萎缩症蛋白1通过抑制氧化应激减少高糖高脂诱导的心肌细胞凋亡
OPA1 ameliorates cardiomyocyte apoptosis induced by high fat and high glucose
via inhibiting oxidative stress- 第三军医大学学报 2017年39卷第2期 页码：151-156
- 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：
裴海峰, E-mail: web2010@foxmail.com Pei Haifeng, E-mail: web2010@foxmail.com
杨大春, E-mail: yangdachun2010@126.com Yang Dachun, E-mail: yangdachun2010@126.com
- 基金信息：国家自然科学基金青年科学基金(81500208);全军医学科技青年培育项目(14QNP050);四川省科技支持计划项目(2015JY0277)
DOI：10.16016/j.1000-5404.201608046
中图分类号： R322.11;R329.26;R589.2纸质出版日期：2017-1-30，
收稿日期：2016-8-8，
录用日期：2016-9-17
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王挺, 杨怡, 田玥, 等. 视神经萎缩症蛋白1通过抑制氧化应激减少高糖高脂诱导的心肌细胞凋亡[J]. 第三军医大学学报, 2017,39(2):151-156.
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, 2017,39(2):151-156.王挺, 杨怡, 田玥, 等. 视神经萎缩症蛋白1通过抑制氧化应激减少高糖高脂诱导的心肌细胞凋亡[J]. 第三军医大学学报, 2017,39(2):151-156. DOI： 10.16016/j.1000-5404.201608046.
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, 2017,39(2):151-156. DOI： 10.16016/j.1000-5404.201608046.
摘要
目的
2
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
2
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
2
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 (
P
＜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(
P
＜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(
P
＜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
2
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
2
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
2
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
2
The apoptotic ratio of cardiomyocytes was gradually increased in a dose- and time-dependent manner (
P
＜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 (
P
＜0.05). Most importantly
the knockdown of OPA1 further aggravated the cardiomyocyte apoptosis and the level of ROS induced by high fat (
P
＜0.05). In contrast
these effects mentioned above were reversed by the application of antioxidant NAC (
P
＜0.05).
Conclusion
2
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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