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高血压盐敏感大鼠的辐射诱导心脏毒性:一项可行性研究。

Radiation-Induced Cardiotoxicity in Hypertensive Salt-Sensitive Rats: A Feasibility Study.

作者信息

An Dayeong, Kriegel Alison, Kumar Suresh, Himburg Heather, Fish Brian, Klawikowski Slade, Rowe Daniel, Lenarczyk Marek, Baker John, Ibrahim El-Sayed

机构信息

Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Deaprtment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

出版信息

Life (Basel). 2025 May 27;15(6):862. doi: 10.3390/life15060862.

DOI:10.3390/life15060862
PMID:40566516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12194215/
Abstract

Radiation therapy (RT) plays a vital role in managing thoracic cancers, though it can lead to adverse effects, including significant cardiotoxicity. Understanding the risk factors like hypertension in RT is important for patient prognosis and management. A Dahl salt-sensitive (SS) female rat model was used to study hypertension effect on RT-induced cardiotoxicity. Rats were fed a high-salt diet to induce hypertension and then divided into RT and sham groups. The RT group received 24 Gy of whole-heart irradiation. Cardiac function was evaluated using MRI and blood pressure measurements at baseline, 8 weeks and 12 weeks post-RT. Histological examination was performed after the last timepoint or animal death. The hypertensive RT rats demonstrated significant decreases in left-ventricular ejection fraction (EF) (45 ± 7.2%) compared to sham (68 ± 7.3%). Furthermore, circumferential (Ecc) and radial (Err) myocardial strains were significantly reduced (Ecc: -7.4 ± 2.0% RT rats vs. -11 ± 2.4% sham; Err: 15 ± 6.5% RT rats vs. 23 ± 8.9% sham). Histological analysis revealed significant pathophysiological remodeling post-RT, including nuclear size, interstitial fibrosis, necrosis, and the presence of inflammatory cells. This study provides valuable insights into the cardiotoxic effects of RT in the context of hypertension, highlighting the potential of using MRI for improved risk assessment with potential for future clinical translation.

摘要

放射治疗(RT)在胸段癌症的治疗中起着至关重要的作用,尽管它可能会导致不良反应,包括严重的心脏毒性。了解放疗中诸如高血压等风险因素对于患者的预后和管理很重要。使用 Dahl 盐敏感(SS)雌性大鼠模型来研究高血压对放疗诱导的心脏毒性的影响。给大鼠喂食高盐饮食以诱发高血压,然后将其分为放疗组和假手术组。放疗组接受 24 Gy 的全心照射。在放疗前基线、放疗后 8 周和 12 周使用 MRI 和血压测量来评估心脏功能。在最后一个时间点或动物死亡后进行组织学检查。与假手术组(68±7.3%)相比,高血压放疗大鼠的左心室射血分数(EF)显著降低(45±7.2%)。此外,圆周(Ecc)和径向(Err)心肌应变也显著降低(Ecc:放疗大鼠为-7.4±2.0%,假手术组为-11±2.4%;Err:放疗大鼠为 15±6.5%,假手术组为 23±8.9%)。组织学分析显示放疗后存在显著的病理生理重塑,包括细胞核大小、间质纤维化、坏死以及炎症细胞的存在。这项研究为高血压背景下放疗的心脏毒性作用提供了有价值的见解,突出了使用 MRI 改善风险评估的潜力以及未来临床转化的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/6e1fd2b6e242/life-15-00862-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/62abc54202fb/life-15-00862-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/8e40c0d42ba8/life-15-00862-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/78b0420ab2c0/life-15-00862-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/a3255ba037cc/life-15-00862-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/1fbcf9578e19/life-15-00862-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/560ac08562cb/life-15-00862-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/6e1fd2b6e242/life-15-00862-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/62abc54202fb/life-15-00862-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/b0221613b546/life-15-00862-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/4047cbff3f14/life-15-00862-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/8e40c0d42ba8/life-15-00862-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/78b0420ab2c0/life-15-00862-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/a3255ba037cc/life-15-00862-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/1fbcf9578e19/life-15-00862-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/560ac08562cb/life-15-00862-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c82e/12194215/6e1fd2b6e242/life-15-00862-g009.jpg

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本文引用的文献

1
Myocardial Contractility Pattern Characterization in Radiation-Induced Cardiotoxicity Using Magnetic Resonance Imaging: A Pilot Study with ContractiX.应用磁共振成像技术对放射性心肌毒性的心肌收缩力模式特征进行描述:使用 ContractiX 的一项初步研究。
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Knockout of the Circadian Clock Protein PER1 (Period1) Exacerbates Hypertension and Increases Kidney Injury in Dahl Salt-Sensitive Rats.敲除昼夜节律蛋白 PER1(Period1)可加重 Dahl 盐敏感性大鼠的高血压并增加肾脏损伤。
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Radiation-Induced Cardiovascular Toxicities.
辐射诱导的心血管毒性。
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Valvular Heart Disease Epidemiology.瓣膜性心脏病流行病学。
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