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STRAP 通过激活 PI3K/PDK1/Akt 信号通路减少心肌细胞内质网应激和细胞凋亡,减轻心肌缺血再灌注损伤。

STRAP reduces endoplasmic reticulum stress and apoptosis in cardiomyocytes and attenuates myocardial ischemia-reperfusion injury by activating PI3K/PDK1/Akt signaling pathway.

机构信息

Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4430-4439. doi: 10.26355/eurrev_202004_21025.

Abstract

OBJECTIVE

Myocardial ischemia-reperfusion injury (MIRI) is a common problem in heart-related diseases. The aim of this study was to explore the protective effects of STRAP on cardiomyocytes in the MIRI process and its mechanisms.

MATERIALS AND METHODS

We used SD rats to construct a MIRI model and increased the expression of STRAP in myocardial tissue by Entranster to detect the effect of STRAP on rat myocardial tissue. In addition, we cultured rat cardiomyocyte cell line H9c2 cells and constructed a hypoxia-reoxygenation model to detect the protective effect of STRAP on H9c2 cells. LY294002, an inhibitor of the PI3K/PDK1/Akt signaling pathway, was used to validate the mechanism by which STRAP protects cardiomyocytes.

RESULTS

Overexpression of STRAP significantly reduced the activity of MDA in myocardial tissue and increased the activity of SOD. STRAP also substantially lowered CK and LDH levels in rat serum and increased Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity. In addition, overexpression of STRAP considerably reduced endoplasmic reticulum stress (ERS) and apoptosis levels in H9c2 cells. However, LY294002 attenuated the protective effect of STRAP on cardiomyocytes.

CONCLUSIONS

STRAP reduces ERS and apoptosis in cardiomyocytes by activating the PI3K/PDK1/Akt signaling pathway, thereby reducing myocardial MIRI.

摘要

目的

心肌缺血再灌注损伤(MIRI)是与心脏相关疾病中的常见问题。本研究旨在探讨 STRAP 在心肌再灌注损伤过程中对心肌细胞的保护作用及其机制。

材料与方法

我们使用 SD 大鼠构建 MIRI 模型,并通过 Entranster 增加心肌组织中 STRAP 的表达,以检测 STRAP 对大鼠心肌组织的影响。此外,我们培养大鼠心肌细胞系 H9c2 细胞,并构建缺氧/复氧模型,以检测 STRAP 对 H9c2 细胞的保护作用。使用 PI3K/PDK1/Akt 信号通路抑制剂 LY294002 验证 STRAP 保护心肌细胞的机制。

结果

STRAP 的过表达显著降低了心肌组织中 MDA 的活性,增加了 SOD 的活性。STRAP 还显著降低了大鼠血清中 CK 和 LDH 的水平,并提高了 Na+-K+-ATPase 和 Ca2+-Mg2+-ATPase 的活性。此外,STRAP 的过表达显著降低了 H9c2 细胞中的内质网应激(ERS)和细胞凋亡水平。然而,LY294002 减弱了 STRAP 对心肌细胞的保护作用。

结论

STRAP 通过激活 PI3K/PDK1/Akt 信号通路减少心肌细胞中的 ERS 和细胞凋亡,从而减轻心肌 MIRI。

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