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铁磁共振成像增强观察脑缺血再灌注损伤中炎症和细胞凋亡的动态变化。

Dynamic changes of inflammation and apoptosis in cerebral ischemia‑reperfusion injury in mice investigated by ferumoxytol‑enhanced magnetic resonance imaging.

机构信息

Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.

MR Scientific Marketing, Siemens Healthcare, Shanghai 201318, P.R. China.

出版信息

Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11921. Epub 2021 Feb 19.

DOI:10.3892/mmr.2021.11921
PMID:33604682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7905325/
Abstract

The inflammatory response and apoptosis are key factors in cerebral ischemia‑reperfusion injury. The severity of the inflammatory reaction and apoptosis has an important impact on the prognosis of stroke. The ultrasmall superparamagnetic iron oxide particle has provided an effective magnetic resonance molecular imaging method for dynamic observation of the cell infiltration process . The aims of the present study were to investigate the inflammatory response of cerebral ischemia‑reperfusion injury in mice using ferumoxytol‑enhanced magnetic resonance imaging, and to observe the dynamic changes of inflammatory response and apoptosis. In the present study a C57BL/6n mouse cerebral ischemia‑reperfusion model was established by blocking the right middle cerebral artery with an occluding suture. Subsequently, the mice were injected with ferumoxytol via the tail vein, and magnetic resonance scanning was performed at corresponding time points to observe the signal changes. Furthermore, blood samples were used to measure the level of serum inflammatory factors, and histological staining was performed to assess the number of iron‑swallowing microglial cells and apoptotic cells. The present results suggested that there was no significant difference in the serum inflammatory factors tumor necrosis factor‑α and interleukin 1β between the middle cerebral artery occlusion (MCAO) and MCAO + ferumoxytol groups injected with ferumoxytol and physiological saline. The lowest signal ratio in the negative enhancement region was decreased 24 h after reperfusion in mice injected with ferumoxytol. The proportion of iron‑swallowing microglial cells and TUNEL‑positive cells were the highest at 24 h after reperfusion, and decreased gradually at 48 and 72 h after reperfusion. Therefore, the present results indicated that ferumoxytol injection of 18 mg Fe/kg does not affect the inflammatory response in the acute phase of cerebral ischemia and reperfusion. Ferumoxytol‑enhanced magnetic resonance imaging can be used as an effective means to monitor the inflammatory response in the acute phase of cerebral ischemia‑reperfusion injury. Furthermore, it was found that activation of the inflammatory response and apoptosis in the acute stage of cerebral ischemia‑reperfusion injury is consistent.

摘要

炎症反应和细胞凋亡是脑缺血再灌注损伤的关键因素。炎症反应和细胞凋亡的严重程度对中风的预后有重要影响。超顺磁性氧化铁纳米颗粒为细胞浸润过程的动态观察提供了一种有效的磁共振分子成像方法。本研究旨在使用超顺磁性氧化铁纳米颗粒增强磁共振成像来研究脑缺血再灌注损伤中的炎症反应,并观察炎症反应和细胞凋亡的动态变化。本研究通过阻塞右大脑中动脉用闭塞缝线建立 C57BL/6n 小鼠脑缺血再灌注模型。随后,通过尾静脉注射超顺磁性氧化铁纳米颗粒,在相应时间点进行磁共振扫描,观察信号变化。此外,采集血液样本测量血清炎症因子水平,并进行组织学染色评估铁吞噬小胶质细胞和凋亡细胞的数量。本研究结果表明,注射超顺磁性氧化铁纳米颗粒和生理盐水的大脑中动脉闭塞(MCAO)和 MCAO+超顺磁性氧化铁纳米颗粒组的血清炎症因子肿瘤坏死因子-α和白细胞介素 1β 无显著差异。再灌注 24 小时后,负增强区域的信号比值降低。再灌注 24 小时后,铁吞噬小胶质细胞和 TUNEL 阳性细胞的比例最高,再灌注 48 和 72 小时后逐渐下降。因此,本研究结果表明,18mgFe/kg 的超顺磁性氧化铁纳米颗粒注射不会影响脑缺血再灌注急性期的炎症反应。超顺磁性氧化铁纳米颗粒增强磁共振成像可作为监测脑缺血再灌注损伤急性期炎症反应的有效手段。此外,还发现脑缺血再灌注损伤急性期炎症反应和细胞凋亡的激活是一致的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/6541ba0df253/mmr-23-04-11921-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/bf07475173ad/mmr-23-04-11921-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/32953c585b3d/mmr-23-04-11921-g04.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/bf07475173ad/mmr-23-04-11921-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/8f3b15f355f2/mmr-23-04-11921-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/744d6af6ffd9/mmr-23-04-11921-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/91b3e7846aa3/mmr-23-04-11921-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/32953c585b3d/mmr-23-04-11921-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/5d046e4022e8/mmr-23-04-11921-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ef/7905325/6541ba0df253/mmr-23-04-11921-g06.jpg

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