Department of Cardiac Surgery, Beijing Chaoyang Hospital, Capital University of Medical Sciences, China.
Department of Cardiac Surgery, Beijing Chaoyang Hospital, Capital University of Medical Sciences, China.
Respir Med. 2020 Jan;161:105852. doi: 10.1016/j.rmed.2019.105852. Epub 2019 Dec 16.
The aim of the study was to investigate the mechanism and effect of FBXL10 in myocardial ischemia reperfusion injury in vivo and in vitro.
The myocardial ischemia reperfusion (I/R) model was established by 30 min of coronary occlusion followed by 2 h of reperfusion in rats. Western blot and TUNEL assay were used to measure the apoptosis during I/R. The expression levels of endoplasmic reticulum related proteins in myocardial tissues and H9c2 cells were detected by immunohistochemistry staining and immunofluorescence staining. Flow cytometry and CCK-8 were used to detect the apoptosis and viability of H9c2 cells.
The results revealed that FBXL10 significantly reduced myocardial infarction, improved the pathological morphology of myocardium, markedly reduced inflammatory response in the myocardial ischemia reperfusion rats. Moreover the expressions of endoplasmic reticulum stress key proteins were caused by I/R were suppressed significantly by FBXL10 treatment, including CHOP, GRP78, ATF4 and p-PERK. Additionally FBXL10 inhibited the expression of endoplasmic reticulum stress key proteins in H/R H9c2 cells. Furthermore, FBXL10 reduced the levels of apoptotic cells and inflammatory response compared with I/R and H/R group.
Taken together, we found that FBXL10 could attenuate I/R injury through inhibiting endoplasmic reticulum stress (ERs).
本研究旨在探讨 FBXL10 在体内和体外心肌缺血再灌注损伤中的作用机制。
通过在大鼠中进行 30 分钟的冠状动脉闭塞后再灌注 2 小时，建立心肌缺血再灌注（I/R）模型。采用 Western blot 和 TUNEL 检测法测量 I/R 期间的细胞凋亡。通过免疫组化染色和免疫荧光染色检测心肌组织和 H9c2 细胞中内质网相关蛋白的表达水平。流式细胞术和 CCK-8 检测 H9c2 细胞的凋亡和活力。
结果表明，FBXL10 可显著减少心肌梗死，改善心肌的病理形态，明显减轻心肌缺血再灌注大鼠的炎症反应。此外，FBXL10 处理可显著抑制 I/R 引起的内质网应激关键蛋白的表达，包括 CHOP、GRP78、ATF4 和 p-PERK。此外，FBXL10 抑制了 H/R H9c2 细胞中内质网应激关键蛋白的表达。此外，与 I/R 和 H/R 组相比，FBXL10 降低了细胞凋亡和炎症反应的水平。
综上所述，我们发现 FBXL10 可以通过抑制内质网应激（ERs）来减轻 I/R 损伤。
