Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest

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書誌事項

公開日
2022-12
資源種別
journal article
権利情報
  • © 2022 The Author(s). Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery.
  • This is an open access article under the CC BY license.
DOI
  • 10.1016/j.xjon.2022.11.001
公開者
Elsevier BV

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説明

OBJECTIVES: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. METHODS: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n=6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. RESULTS: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P=.0021] and CN vs CH [P<.001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51±0.71 vs 0.82±0.32; P=.0414 and cystatin C: 1.48±0.39 vs 0.71±0.26; P=.0015). There was no significant difference between QN and QH. CONCLUSIONS: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future.

収録刊行物

  • JTCVS Open

    JTCVS Open 12 201-210, 2022-12

    Elsevier BV

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