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埃索美拉唑抑制内质网应激,改善心肌缺血再灌注损伤。

Esomeprazole inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia-reperfusion injury.

机构信息

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

出版信息

Biochem Biophys Res Commun. 2022 Oct 30;627:84-90. doi: 10.1016/j.bbrc.2022.08.013. Epub 2022 Aug 13.

Abstract

Proton pump inhibitors (PPIs) are often prescribed in association with clopidogrel and aspirin to patients with myocardial infraction (MI), but their effects on heart is controversial. The purpose of this study was to investigate the effects and potential mechanism of omeprazole (OME) and esomeprazole (ESO) in myocardial ischemia reperfusion (I/R) injury. In the present study, mice were treated with OME, ESO or vehicle for 3 weeks and then subjected to myocardial I/R or sham surgery. At 1 day after surgery, echocardiography was performed to access cardiac injury. Hematoxylin and eosin (H&E) staining was performed to evaluate cardiomyocyte morphology. The IL1β was evaluated by Immunohistochemistry (IHC). Elisa was used to detect cTnt content in serum. The expression of CD86, CD206, CHOP, ATF6, eIF2α and p eIF2α were determined by Western blot (WB). The result showed that ESO markedly improved the left ventricular ejection fraction (LVEF), shortening fraction (FS), suppressed inflammatory infiltration, endoplasmic reticulum stress (ERS) and decreased proinflammatory macrophages in I/R hearts, while OME had no significant effects on cardiac function, inflammation and ERS in the I/R heart. In conclusion, ESO but not OME pretreatment reduces the proportion of proinflammatory macrophages, inhibits endoplasmic reticulum stress, and alleviates I/R injury in mice, indicating that ESO maybe a more proper PPI than OME for application in I/R injury.

摘要

质子泵抑制剂(PPIs)常与氯吡格雷和阿司匹林联合用于心肌梗死(MI)患者,但它们对心脏的影响存在争议。本研究旨在探讨奥美拉唑(OME)和埃索美拉唑(ESO)在心肌缺血再灌注(I/R)损伤中的作用及潜在机制。在本研究中,小鼠用 OME、ESO 或载体处理 3 周,然后进行心肌 I/R 或假手术。手术后 1 天,进行超声心动图评估心脏损伤。进行苏木精和伊红(H&E)染色评估心肌细胞形态。通过免疫组化(IHC)评估 IL1β。用 Elisa 检测血清中 cTnt 含量。通过 Western blot(WB)检测 CD86、CD206、CHOP、ATF6、eIF2α 和 p eIF2α 的表达。结果表明,ESO 显著改善了 I/R 心脏的左心室射血分数(LVEF)、缩短分数(FS),抑制了炎症浸润、内质网应激(ERS)和促炎巨噬细胞的增加,而 OME 对 I/R 心脏的心脏功能、炎症和 ERS 没有显著影响。总之,ESO 预处理而非 OME 预处理可降低促炎巨噬细胞的比例,抑制内质网应激,减轻小鼠的 I/R 损伤,表明 ESO 可能是比 OME 更合适的 PPI,可用于 I/R 损伤。

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