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|本期目录/Table of Contents|

心肌缺血/再灌损伤时TXNIP表达水平升高并增加心肌自噬

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第5期
页码:
497-502
栏目:
基础研究
出版日期:
2018-06-25

文章信息/Info

Title:
TXNIP level increases during myocardial ischemia/reperfusion injury and aggravates autophagy
作者:
戴 一1; 褚 超1; 高 超2
（1.西安交通大学第一附属医院心血管内科，陕西 西安 710061；2.第四军医大学西京医院心血管内科，陕西 西安 710032）
Author(s):
DAI Yi1;  CHU Chao1;  GAO Chao2
(1.Department of Cardiology, First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; 2.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
心肌缺血/再灌注; 自噬; 硫氧还蛋白相互结合蛋白
Keywords:
TXNIP;  Myocardial ischemia/reperfusion;  Autophagy;  Cardiac dysfunction
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的 探讨心肌缺血/再灌注(MI/R)时硫氧还蛋白相互结合蛋白(TXNIP)表达及对心肌细胞自噬水平的影响。方法 构建TXNIP敲除鼠及TXNIP过表达小鼠，制作上述小鼠MI/R模型，观察MI/R后心肌TXNIP表达水平是否与心肌损伤及自噬有关。结果 与假手术组（Sham）小鼠相比，小鼠心肌TXNIP表达水平在缺血及再灌注损伤过程中持续升高（P<0.01）。在小鼠MI/R后，心脏超声证实与野生型（WT）小鼠相比，TXNIP过表达小鼠LVEF(%)值更低（P<0.05）；伊文氏蓝/TTC染色同样证实TXNIP过表达小鼠心肌梗死面积更大（P<0.05）。而TXNIP敲除鼠MI/R后心脏LVEF(%)值（P<0.05）及心肌梗死面积（P<0.05）均较WT小鼠显著减轻。通过免疫印迹（LC3II/LC3I及P62表达）及电子显微镜观察自噬小体检测发现，相比WT小鼠，TXNIP敲除小鼠心肌自噬程度更轻（P<0.05），TXNIP过表达小鼠则心肌自噬程度更重（P<0.05）。结论 上述结果证实了在MI/R后TXNIP升高导致心脏功能的降低，心肌梗死面积的增加及心肌细胞自噬的增多。
Abstract:
AIM To elucidate a possible relationship between TXNIP levels and increased activation of autophagosomes during myocardial ischemia/reperfusion (MI/R) injury. METHODS Using a MI/R mice model in TXNIP knockout and overexpressed mice, the present investigation observed whether TXNIP levels are linked to autophagy levels and MI/R injury. RESULTS Compared to Sham mice, the level of TXNIP increased during MI/R (P<0.01). After MI/R, echocardiography confirmed that TXNIP overexpression aggravated MI/R-induced cardiac dysfunction by lower LVEF% (P<0.05) and Evansblue/TTC staining revealed that TXNIP overexpression aggravated myocardium infarct size (P<0.05). In comparison, TXNIP knockout mice showed reduced MI/R-induced cardiac dysfunction by LVEF% (P<0.05) and infarct size (P<0.05) compared with wild-type (WT) mice. Further, the present investigation found that elevated TXNIP enhanced MI/R-induced autophagy activation, demonstrated by increased LC3 II/I ratio and increased MI/R-induced autophagosome number. CONCLUSION Elevated TXNIP during MI/R aggravates MI/R-induced cardiac dysfunction, enlarges infarct size, and increases autophagy levels.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2017-08-05.基金项目：国家自然科学基金项目资助（81570381）；国家自然科学基金青年项目(81600281) 通讯作者：高超，主治医师，博士，主要从事心血管病临床研究 Email：charleygao@163.com 作者简介：戴一，主治医师，博士生 Email：wujingyiyuandy@163.com
更新日期/Last Update: 1900-01-01