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米诺环素对兔缺血/再灌注损伤的心脏保护作用:体内 In-GSAO SPECT 检测细胞死亡。

Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury: Detection of cell death by in vivo In-GSAO SPECT.

机构信息

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.

出版信息

J Nucl Cardiol. 2018 Feb;25(1):94-100. doi: 10.1007/s12350-017-1031-8. Epub 2017 Aug 24.

DOI:10.1007/s12350-017-1031-8
PMID:28840574
Abstract

BACKGROUND

Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion.

METHODS

Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization.

RESULTS

Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals.

CONCLUSIONS

This study demonstrates cardioprotection by minocycline in a clinically translatable protocol.

摘要

背景

临床前研究表明米诺环素可预防心肌缺血/再灌注损伤。在这些研究中,米诺环素是在缺血前给予的,而这种情况在临床实践中很少发生。本研究旨在评估再灌注时米诺环素治疗的心脏保护作用。

方法

兔子经历心肌缺血/再灌注损伤,并在再灌注时接受静脉内米诺环素(n=8)或生理盐水(n=8)治疗。通过注射铟-111 标记的 4-(N-(S-谷胱甘酰基乙酰基)氨基)苯砷酸(In-GSAO)后,通过体内微 SPECT/CT 评估心脏细胞死亡。之后,取出心脏进行离体成像、γ计数和组织病理学特征分析。

结果

微 SPECT/CT 成像显示心肌损伤。危险区域的 GSAO 摄取定量(表示为每克注射剂量的百分比,%ID/g)在米诺环素治疗组低于生理盐水对照组(0.32±0.13% vs 0.48±0.15%,P=0.04)。TUNEL 染色证实米诺环素治疗组的细胞死亡减少。

结论

这项研究在一种具有临床转化意义的方案中证明了米诺环素的心脏保护作用。

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Minocycline repurposing in critical illness: focus on stroke.米诺环素在危重病中的再利用:关注中风。
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Optical imaging of cell death in traumatic brain injury using a heat shock protein-90 alkylator.利用热休克蛋白 90 烷化剂对创伤性脑损伤细胞死亡的光学成像
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