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橄榄叶提取物通过内质网应激途径对丙烯醛加重的心肌梗死的保护作用。

Protective Effects of Olive Leaf Extract on Acrolein-Exacerbated Myocardial Infarction via an Endoplasmic Reticulum Stress Pathway.

机构信息

Department of Nutrition and Food Hygiene, Nanjing Medical University, Nanjing 211166, China.

Department of Cardiology, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210000, China.

出版信息

Int J Mol Sci. 2018 Feb 7;19(2):493. doi: 10.3390/ijms19020493.

Abstract

Many studies reported that air pollution particulate matter (PM) exposure was associated with myocardial infarction (MI). Acrolein representing the unsaturated aldehydes, the main component of PM, derives from the incomplete combustion of wood, plastic, fossil fuels and the main constitute of cigarette smoking. However, the effect of acrolein on MI remains not that clear. In the current study, the effect of acrolein-exacerbated MI was investigated. In vivo, male Sprague-Dawley rats received olive leaf extract (OLE) followed by acrolein, then isoprenaline (ISO) was received by subcutaneous injection to induce MI. Results showed that the expression levels of GRP78 and CHOP, two major components of endoplasmic reticulum (ER) stress were higher in the combination of acrolein and ISO than those in ISO treatment. The apoptosis marker, Bax, was also higher while the anti-apoptosis indicator, Bcl2 expression was lower both at protein and mRNA levels in the combination group. Also, the acrolein-protein adducts and myocardial pathological damage increased in the combination of acrolein and ISO relative to the ISO treatment. Besides, cardiac parameters, ejection fraction (EF) and fractional shortening (FS) were reduced more significantly when acrolein was added than in ISO treatment. Interestingly, all the changes were able to be ameliorated by OLE. Since hydroxytyrosol (HT) and oleuropein (OP) were the main components in OLE, we next investigated the effect of HT and OP on cardiomyocyte H9c2 cell apoptosis induced by acrolein through ER stress and Bax pathway. Results showed that GRP78, CHOP and Bax expression were upregulated, while Bcl2 expression was downregulated both at the protein and mRNA levels, when the H9c2 cells were treated with acrolein. In addition, pretreatment with HT can reverse the expression of GRP78, CHOP, Bax and Bcl2 on the protein and mRNA levels, while there was no effect of OP on the expression of GRP78 and CHOP on the mRNA levels. Overall, all these results demonstrated that OLE and the main components (HT and OP) could prevent the negative effects of acrolein on myocardium and cardiomyocytes.

摘要

许多研究报告指出,空气污染颗粒物(PM)暴露与心肌梗死(MI)有关。丙烯醛代表不饱和醛,是 PM 的主要成分,来源于木材、塑料、化石燃料的不完全燃烧以及吸烟的主要成分。然而,丙烯醛对 MI 的影响尚不清楚。在本研究中,研究了丙烯醛加重 MI 的作用。在体内,雄性 Sprague-Dawley 大鼠先给予橄榄叶提取物(OLE),然后皮下注射异丙肾上腺素(ISO)诱导 MI。结果表明,与 ISO 处理相比,丙烯醛和 ISO 的组合中内质网(ER)应激的两个主要成分 GRP78 和 CHOP 的表达水平更高。凋亡标志物 Bax 的蛋白和 mRNA 水平均升高,而抗凋亡标志物 Bcl2 的表达水平均降低。组合组中的丙烯醛蛋白加合物和心肌病理损伤也增加。此外,与 ISO 处理相比,当加入丙烯醛时,心脏参数射血分数(EF)和缩短分数(FS)降低更为明显。有趣的是,所有这些变化都可以通过 OLE 得到改善。由于羟基酪醇(HT)和橄榄苦苷(OP)是 OLE 的主要成分,我们接下来研究了 HT 和 OP 通过 ER 应激和 Bax 途径对丙烯醛诱导的心肌细胞 H9c2 细胞凋亡的影响。结果表明,当 H9c2 细胞用丙烯醛处理时,GRP78、CHOP 和 Bax 的蛋白和 mRNA 水平上调,而 Bcl2 的蛋白和 mRNA 水平下调。此外,HT 的预处理可以逆转 GRP78、CHOP、Bax 和 Bcl2 的蛋白和 mRNA 水平的表达,而 OP 对 GRP78 和 CHOP 的 mRNA 水平的表达没有影响。总的来说,所有这些结果表明,OLE 及其主要成分(HT 和 OP)可以防止丙烯醛对心肌和心肌细胞的负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/5855715/0255b44a60fd/ijms-19-00493-g001.jpg

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