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。
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 Evans- blue/TYC 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.
作者
戴一
褚超
高超
DAI Yi;CHU Chao;GAO Chao(Department of Cardiology,First Affiliated Hospital,Xi ＇an Jiaotong University,Xi＇an 710061,Sham~i,China;Department of Cardiology,Xijing Hospital,Fourth Military Medical University,Xi＇ an 710032,Shaanxi,China)
出处
《心脏杂志》
CAS
2018年第5期497-502,共6页
Chinese Heart Journal
基金
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)
