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首页> 外文期刊>American Journal of Physiology >Cardiac responses to hypoxia and reoxygenation in Drosophila
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Cardiac responses to hypoxia and reoxygenation in Drosophila

机译：果蝇对缺氧和雷诺的心脏反应

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An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-alpha), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation.
机译：足够的氧气供应对于所有组织的存活是重要的，但对于具有高能量需求的组织尤其重要，例如心脏。组织氧气不足发生在各种条件下，包括高海拔，胚胎和胎儿发育，炎症和血栓疾病，通常影响多器官系统。心脏对缺氧的反应和适应在人体心血管和肺部疾病中特别相关，其中缺氧暴露的影响可以在严重程度从瞬态到持久性。本研究使用遗传模型系统果蝇调查心脏反应对急性（30分钟），持续（18小时）和慢性（3WK）缺氧进行雷诺基化。虽然野生型苍蝇的心脏在急性缺氧后迅速恢复，但暴露于持续或慢性缺氧，在重新结合时显着受到心脏功能。来自辛巴突变的心脏，缺氧诱导因子α亚基（HIF-α）的果蝇同源物，表现出缺氧的心输出夸张的减少。在低氧环境中选择缺氧的苍蝇中的心脏功能，在低氧环境中为生存期间选择，揭示了心率降低的心脏输出，与其常氧对照相比，分数缩短。缺氧选择的苍蝇也具有较小的心脏，肌原纤维紊乱和增加的细胞外胶原沉积，与观察到的收缩性降低一致。本研究表明，较长持续时间缺氧侮辱对介导的心脏功能产生有害影响，部分地由SIMA提出果蝇模型，用于对缺氧和雷诺的遗传分析的遗传分析。

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