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Cardiac screening of intact Drosophila melanogaster larvae under exposure to aqueous and gaseous toxins in a microfluidic device

机译:在微流体装置暴露于水溶液和气态毒素下的完整果蝇黑素转基营类幼虫的心脏筛选

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摘要

Drosophila melanogaster is one of the promising model organisms for investigation of human diseases such as cardiac disorders. However, intact (not dissected) Drosophila larvae have not been extensively used as models in cardiac toxicity assays due to many challenges associated with assessment of their heart activities in the intact mode (i.e., heartrate monitoring of alive larva under exposure to aqueous and gaseous reagents). These challenges include the need for precise spatiotemporal control of stimulus exposure to posterior spiracles (i.e., breathing valves) and full immobilization of larvae in favorable orientations to monitor the heart under a microscope. In this paper, we not only present a novel microfluidic device that is capable of loading, orientating and immobilizing the larva reversibly in a chip, but also demonstrate for the first time the transient effects of toxic liquids (e.g., sodium azide) and gases (e.g., oxygen and carbon dioxide) at various concentrations on the heart of intact Drosophila larvae. The results demonstrated that cardiac activity increase (with excess oxygen) or arrest (with sodium azide, carbon dioxide, or lack of oxygen) are highly dependent on the concentration of the stimuli, but heart recovery after removal of chemicals is independent of chemical concentration. The presented device can be used for investigation of biological pathways underlying these responses and also for screening of various chemicals such as pharmaceutical, toxicological, and agricultural compounds on the cardiac system of intact Drosophila melanogaster or other compatible insect models. This will open new windows of opportunity in drug discovery and toxicology applications.
机译:果蝇Melanogaster是有前途的模型生物之一,用于调查人类疾病,如心脏病。然而,由于与在完整模式中对其心脏活动的评估相关的许多挑战(即,在暴露于水性和气态试剂的情况下,培养对含水和气态试剂的活性幼虫的评估相关的许多挑战)。这些挑战包括对后刺刺肌(即呼吸阀)的精确时尚控制的需要,以及幼虫的全固定在显微镜下监测心脏。在本文中,我们不仅提出了一种新型微流体装置,其能够在芯片中可逆地装载,取向和固定幼虫,而且还证明了毒性液体(例如,叠氮化钠)和气体的瞬态影响(例如,氧气和二氧化碳)在完整的果蝇幼虫的全部浓度下。结果表明,心脏活性增加(用过量的氧气)或捕获(用叠氮化物,二氧化碳或缺氧)高度依赖于刺激的浓度,但除去化学物质后的心脏恢复与化学浓度无关。本发明的装置可用于研究这些反应的基础途径,并且还用于筛选各种化学品,如药物,毒理学和农业化合物的完整果蝇黑色素素或其他相容昆虫模型的心脏系统。这将在药物发现和毒理学应用中开放新的机会Windows。

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  • 来源
    《RSC Advances》 |2016年第70期|共11页
  • 作者单位

    York Univ Dept Mech Engn BRG 433B 4700 Keele St Toronto ON M3J 1P3 Canada;

    York Univ Dept Mech Engn BRG 433B 4700 Keele St Toronto ON M3J 1P3 Canada;

    York Univ Dept Mech Engn BRG 433B 4700 Keele St Toronto ON M3J 1P3 Canada;

    York Univ Dept Mech Engn BRG 433B 4700 Keele St Toronto ON M3J 1P3 Canada;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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