PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
未经证实：急性肾损伤是心血管手术后需要停循环的严重并发症。据报道,可以通过刺激位于下丘脑的特定神经元(静止诱导神经元诱导的低代谢[QIH])将小鼠诱导为冬眠样代谢状态。这里,我们使用转基因小鼠模型研究了QIH在实验性循环阻滞中改善急性肾损伤的功效。
UNASSIGNED：我们在遗传上制备了可以条件诱导QIH的小鼠（QIH就绪小鼠）。将小鼠分为4组（每组n=6）：QIH准备正常体温（QN），QIH准备低温（QH），控制正常体温（CN），控制低温（CH）。QIH诱导后，进行左开胸和降主动脉交叉夹闭。再灌注后,我们收集肾脏并评估组织学变化和血清生化标志物，特别是中性粒细胞明胶酶相关脂质运载蛋白和胱抑素C，提示早期肾损伤。
UNASSIGNED：正常体温的肾小管损伤评分高于低温组（QNvsQH[P=.0021]和CNvsCH[P<.001]）。QN显示中性粒细胞明胶酶相关脂质运载蛋白和胱抑素C水平低于CN（中性粒细胞明胶酶相关脂质运载蛋白：CNvsQN：1.51±0.71vs0.82±0.32；P=.0414，胱抑素C：1.48±0.39vs0.71±0.26；P=.0015）。QN与QH之间无显著差别。
未经证实：QIH部分改善了小鼠缺血模型中的急性肾损伤，即使在正常体温下也是如此。QIH可能是一种有希望的方法，可以在将来实现足够的肾脏保护而不会出现低温循环停滞。
UNASSIGNED：我们在遗传上制备了可以条件诱导QIH的小鼠（QIH就绪小鼠）。将小鼠分为4组（每组n=6）：QIH准备正常体温（QN），QIH准备低温（QH），控制正常体温（CN），控制低温（CH）。QIH诱导后，进行左开胸和降主动脉交叉夹闭。再灌注后,我们收集肾脏并评估组织学变化和血清生化标志物，特别是中性粒细胞明胶酶相关脂质运载蛋白和胱抑素C，提示早期肾损伤。
UNASSIGNED：正常体温的肾小管损伤评分高于低温组（QNvsQH[P=.0021]和CNvsCH[P<.001]）。QN显示中性粒细胞明胶酶相关脂质运载蛋白和胱抑素C水平低于CN（中性粒细胞明胶酶相关脂质运载蛋白：CNvsQN：1.51±0.71vs0.82±0.32；P=.0414，胱抑素C：1.48±0.39vs0.71±0.26；P=.0015）。QN与QH之间无显著差别。
未经证实：QIH部分改善了小鼠缺血模型中的急性肾损伤，即使在正常体温下也是如此。QIH可能是一种有希望的方法，可以在将来实现足够的肾脏保护而不会出现低温循环停滞。
