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外源性甘丙肽片段对心肌缺血/再灌注损伤的保护作用

Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment.

作者信息

Timotin Andrei, Pisarenko Oleg, Sidorova Maria, Studneva Irina, Shulzhenko Valentin, Palkeeva Marina, Serebryakova Larisa, Molokoedov Aleksander, Veselova Oksana, Cinato Mathieu, Tronchere Helene, Boal Frederic, Kunduzova Oksana

机构信息

National Institute of Health and Medical Research (INSERM), Toulouse, France.

University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.

出版信息

Oncotarget. 2017 Mar 28;8(13):21241-21252. doi: 10.18632/oncotarget.15071.

DOI:10.18632/oncotarget.15071
PMID:28177906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5400580/
Abstract

BACKGROUND AND PURPOSE

Galanin is a multifunctional neuropeptide with pleiotropic roles. The present study was designed to evaluate the potential effects of galanin (2-11) (G1) on functional and metabolic abnormalities in response to myocardial ischemia-reperfusion (I/R) injury.

EXPERIMENTAL APPROACH

Peptide G1 was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase method. The chemical structure was identified by 1H-NMR spectroscopy and mass spectrometry. Experiments were conducted using a rat model of I/R injury in vivo, isolated perfused rat hearts ex vivo and cultured rat cardiomyoblast H9C2 cells in vitro. Cardiac function, infarct size, myocardial energy metabolism, hemodynamic parameters, plasma levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured in order to evaluate the effects of G1 on myocardial I/R injury.

KEY RESULTS

Treatment with G1 increased cell viability in a dose-dependent manner, inhibited cell apoptosis and excessive mitochondrial reactive oxygen species (ROS) production in response to oxidative stress in H9C2 cells. Pre- or postischemic infusion of G1 enhanced functional and metabolic recovery during reperfusion of the ischemic isolated rat heart. Administration of G1 at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats subjected to myocardial I/R injury.

CONCLUSIONS AND IMPLICATIONS

These data provide the first evidence for cardioprotective activity of galanin G1 against myocardial I/R injury. Therefore, peptide G1 may represent a promising treatment strategy for ischemic heart disease.

摘要

背景与目的

甘丙肽是一种具有多种功能的神经肽，发挥着多效性作用。本研究旨在评估甘丙肽（2 - 11）（G1）对心肌缺血再灌注（I/R）损伤所致功能和代谢异常的潜在影响。

实验方法

采用基于9 - 芴甲氧羰基（Fmoc）的固相法合成肽G1。通过1H - NMR光谱和质谱鉴定其化学结构。体内实验使用I/R损伤大鼠模型，体外实验采用离体灌注大鼠心脏和体外培养的大鼠心肌成纤维细胞H9C2。测量心脏功能、梗死面积、心肌能量代谢、血流动力学参数、血浆肌酸激酶 - MB（CK - MB）和乳酸脱氢酶（LDH）水平，以评估G1对心肌I/R损伤的影响。

主要结果

G1处理以剂量依赖方式增加细胞活力，抑制H9C2细胞因氧化应激引起的细胞凋亡和过量线粒体活性氧（ROS）生成。缺血前或缺血后输注G1可增强缺血离体大鼠心脏再灌注期间的功能和代谢恢复。在再灌注开始时给予G1可显著减小心肌I/R损伤大鼠的梗死面积以及降低血浆CK - MB和LDH水平。

结论与意义

这些数据首次证明了甘丙肽G1对心肌I/R损伤具有心脏保护活性。因此，肽G1可能是一种有前景的缺血性心脏病治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/baff62d9e8b2/oncotarget-08-21241-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/2a68e2a18909/oncotarget-08-21241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/e3d17793a2d9/oncotarget-08-21241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/baff62d9e8b2/oncotarget-08-21241-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/1db30548593b/oncotarget-08-21241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/620f8fcaf2b3/oncotarget-08-21241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/8bf0df0efb7e/oncotarget-08-21241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/232e8a59df1f/oncotarget-08-21241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/2a68e2a18909/oncotarget-08-21241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/e3d17793a2d9/oncotarget-08-21241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5400580/baff62d9e8b2/oncotarget-08-21241-g007.jpg

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