左旋谷氨酰胺对缺血大鼠心脏模型的心脏保护作用

IF 2.9 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Microvascular research Pub Date : 2024-11-19 DOI:10.1016/j.mvr.2024.104764
Akiko Kawakami , Hiroaki Sato , Yosuke Nakadate , Patricia Roque , Arkady Khoutorsky , Takashi Matsukawa , Thomas Schricker
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引用次数: 0

摘要

简介:在缺血再灌注损伤模型中,l-谷氨酰胺已被证明具有心脏保护作用。然而,在早期再灌注前和再灌注期间给予 l-谷氨酰胺时,其潜在的心脏保护作用尚未得到研究:本研究假设,在心肌缺血前后给予 l-谷氨酰胺比仅在缺血后给予 l-谷氨酰胺能更好地保护心脏。使用 Langendorff 系统将 18 只雄性大鼠的心脏暴露于 15 分钟的心肌缺血,并将其随机分配到三组,每组六只。第一组在缺血前 20 分钟和再灌注 20 分钟期间接受克雷布斯-亨斯勒(KH)缓冲液(对照组),第二组在再灌注期间接受含有 2.5 mmol・L-1 谷氨酰胺的 KH 缓冲液(Post-Gln 组),第三组在缺血前和缺血后接受含有谷氨酰胺的 KH 缓冲液(Pre + Post-Gln)。记录再灌注后 5、10、15 和 20 分钟的血液动力学指标,如左心室压力发展的最大导数(LV dP/dt max)。再灌注20分钟后,通过Western印迹技术测定心肌中O-连环β-N-乙酰葡糖胺(O-GlcNAc)和热休克蛋白70(HSP70)的水平:结果:再灌注10分钟后,与再灌注后组相比,再灌注前+再灌注后组的左心室dp/dt max明显升高,且在所有时间点均明显高于对照组。O-GlcNAc 的心肌表达在 Gln 前+Gln 后组有所增加(P 结论:O-GlcNAc 的表达在 Gln 前+Gln 后组明显高于对照组):在这种心肌骤停模型中,缺血前后给予 l-谷氨酰胺可改善心脏功能,表明其具有心脏保护作用,这可能是由 O-GlcNAc 介导的。
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Cardioprotective effects of l-glutamine in an ischemic rat heart model

Introduction

l-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not been studied.

Methods

This study hypothesized that l-glutamine administered before and after myocardial ischemia provides better cardioprotection than when administered after ischemia only. Eighteen male rat hearts were exposed to 15 min of ischemia using the Langendorff system and randomly assigned to three groups of six each. Group one received Krebs-Henseleit (KH) buffer over 20 min before ischemia and during 20 min of reperfusion (Control), group two received KH buffer containing 2.5 mmol・L−1 glutamine during reperfusion (Post-Gln) and group three was given KH buffer containing glutamine before and after the ischemic insult (Pre + Post-Gln). Indicators of hemodynamics such as maximum left ventricular derivative of pressure development (LV dP/dt max) were recorded at 5, 10, 15 and 20 min post-reperfusion. Myocardial levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and heat shock protein 70 (HSP70) were measured by Western blotting technique after 20 min of reperfusion.

Results

The LV dp/dt max in the Pre + Post-Gln group was significantly elevated as compared to the Post-Gln group after 10 min of reperfusion and was significantly higher than in the control group at all-time points. Myocardial expression of O-GlcNAc was increased in the Pre + Post-Gln group (P < 0.01 vs. control) without showing any differences in HSP70.

Conclusion

In this model of stunned myocardium, pre- and post-ischemic administration of l-glutamine improved cardiac function indicating cardioprotective effects, possibly mediated by O-GlcNAc.
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来源期刊
Microvascular research
Microvascular research 医学-外周血管病
CiteScore
6.00
自引率
3.20%
发文量
158
审稿时长
43 days
期刊介绍: Microvascular Research is dedicated to the dissemination of fundamental information related to the microvascular field. Full-length articles presenting the results of original research and brief communications are featured. Research Areas include: • Angiogenesis • Biochemistry • Bioengineering • Biomathematics • Biophysics • Cancer • Circulatory homeostasis • Comparative physiology • Drug delivery • Neuropharmacology • Microvascular pathology • Rheology • Tissue Engineering.
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