利用斑马鱼胚胎模型对缓解心力衰竭的新型一氧化氮释放纳米粒子进行体内测试

IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Maram Hasan , Hadeel T. Zedan , Dana Al-Fakhroo , Hend Elsayed Ibrahim , Sumaya Ibrahim Abiib , Ibrahim M. El-Sherbiny , Huseyin C. Yalcin
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引用次数: 0

摘要

心力衰竭(HF)是一种多因素、异质性的全身性疾病,被认为是全球死亡和发病的主要原因之一。众所周知,内皮功能障碍(ED)在心脏病病因中扮演着重要角色。一氧化氮(NO)在血液中的生物利用率降低会导致血管收缩和 ED。许多研究表明,在慢性高血压患者中,由内皮细胞介导的外周动脉血管舒张功能减弱。随着纳米医学的发展,纳米技术可以为借助纳米颗粒(NPs)输送外源性 NO 治疗 ED 提供适当的解决方案。超顺磁性氧化铁纳米粒子(SPIONs)的特性可实现被动和主动给药。这促使我们研究新开发的水凝胶纳米颗粒(NO-RPs)在输送和持续释放氮氧化物气体以缓解心衰斑马鱼模型的心衰和炎症方面的功效。水凝胶 NO-RPs 含有 SPIONS 和 NO 前体。NO-RPs 可持续释放 NO(4200 秒),克服了 NO 在体内半衰期短的问题,有望改善 NO 生物利用率降低的问题及其对内皮和心脏功能障碍的影响。本研究使用斑马鱼胚胎作为动物模型,以确定 SPIONs 负载 NO-RPs 对心血管系统的影响。将 24hpf 胚胎暴露于马兜铃酸(AA)(0.25、0.5 μM)中 8 小时,然后用 SPIONs-loaded NO-RPs(0.25、0.5 mg/ml)处理 48 小时,诱导心力衰竭,实验组包括:对照组(未处理的健康斑马鱼胚胎)、AA 损伤斑马鱼胚胎(HF)模型和 NO-RP 处理的 HF 斑马鱼胚胎。存活率在72hpf时进行评估。还通过分析心脏参数来评估心脏功能,包括心跳、主要血管初级贲门静脉和背主动脉(PCV & DA)直径、PCV & DA血管中的血流速度、心输出量和PCV & DA剪应力。所有心脏参数均借助 Viewpoint 公司的 MicroZebraLab 血流分析软件进行分析。此外,我们还研究了所开发的 NO-RPs 对某些促炎标志物 mRNA 表达的分子影响:IL-6和Cox-2。我们的研究结果表明,NO-RPs 能显著提高心衰斑马鱼模型的存活率,并通过增强斑马鱼胚胎的血流灌注逆转心衰。此外,RT-PCR 结果显示,NO-RPs 能显著降低心衰斑马鱼模型中促炎标志物(lL-6&COX-2)的表达。我们的研究证实,所开发的 SPIONs 负载 NO-RPs 是缓解高频斑马鱼模型心衰和炎症的有效工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vivo testing of novel nitric oxide-releasing nanoparticles for alleviating heart failure using the zebrafish embryo model

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 μM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model.

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来源期刊
Nitric oxide : biology and chemistry
Nitric oxide : biology and chemistry 生物-生化与分子生物学
CiteScore
7.50
自引率
7.70%
发文量
74
审稿时长
52 days
期刊介绍: Nitric Oxide includes original research, methodology papers and reviews relating to nitric oxide and other gasotransmitters such as hydrogen sulfide and carbon monoxide. Special emphasis is placed on the biological chemistry, physiology, pharmacology, enzymology and pathological significance of these molecules in human health and disease. The journal also accepts manuscripts relating to plant and microbial studies involving these molecules.
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