Uninephrectomy (UNX) is known to result in structural and metabolic changes to the remaining kidney, although it is uncertain if this alters the mitochondrial redox state and how soon such changes may occur. A custom‐designed fluorescence cryo‐imaging technique was used to quantitatively assess the effect of UNX by measuring the levels of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the remaining kidney. Kidneys were snap‐frozen 3 days following UNX, and the intrinsic fluorescence of NADH and FAD were optically acquired. The 3D images were created to characterize the NADH/FAD redox ratios (RR) of the right kidneys, which underwent UNX and the remaining kidneys 3 days following UNX. Both the NADPH‐oxidases (Nox2 and Nox4) and the mitochondria are the main sources of reactive oxygen species (ROS) production in tubular epithelial cells. Responses to the UNX were obtained in kidneys of normal Sprague Dawley (SD) rats, Dahl salt‐sensitive (SS) rats and SS rats in which NADPH‐oxidase isoform 4 (Nox4) was knocked out (SS^Nox4−/−). The results found that each of the strains exhibited similar increase in kidney weights averaging 17% after 3 days of UNX. SD and SS^Nox4−/−rats both exhibited global reductions of the RR (P < .05) with a similar tendency observed in SS rats (P < .08), indicating increased ROS production. The unexpected reduction of the RR in the remnant kidneys of SS^Nox4−/− rats indicates that mechanisms independent of H₂O₂ produced from Nox4 may be responsible for this global increase of ROS. We propose that the reduced RR was largely a consequence of enhanced mitochondrial bioenergetics due to increased tubular workload of the remaining kidney. The data indicate that mitochondria become the dominant source of increased ROS following UNX and could represent an important hypertrophic signaling mechanism.

中文翻译：

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光学成像对单肾切除术对大鼠肾脏代谢状态的早期影响。

众所周知，单肾切除术（UNX）会导致剩余肾脏的结构和代谢改变，尽管尚不确定这是否会改变线粒体的氧化还原状态以及这种改变可能发生的时间。通过测量剩余肾脏中烟酰胺腺嘌呤二核苷酸（NADH）和黄素腺嘌呤二核苷酸（FAD）的水平，使用定制设计的荧光冷冻成像技术定量评估UNX的效果。UNX 3天后将肾脏速冻，并光学获取NADH和FAD的固有荧光。创建3D图像以表征右肾的NADH / FAD氧化还原比（RR），右肾在UNX后3天接受UNX治疗，其余肾脏则接受。NADPH氧化酶（Nox2和Nox4）和线粒体都是肾小管上皮细胞中活性氧（ROS）产生的主要来源。在正常Sprague Dawley（SD）大鼠，Dahl盐敏感（SS）大鼠和敲除NADPH-氧化酶同工型4（Nox4）的SS大鼠的肾脏中获得对UNX的应答^Nox4-/-）。结果发现，在UNX 3天后，每个菌株的肾脏重量均表现出相似的增加，平均为17％。SD和SS ^Nox4-/-大鼠均表现出RR整体降低（P  <.05），在SS大鼠中观察到相似的趋势（P  <.08），表明ROS产生增加。SS ^Nox4-/-大鼠残余肾脏中RR的意外降低表明机制独立于H ₂ O ₂Nox4产生的产物可能是ROS在全球增长的原因。我们认为降低的RR主要是由于增加的剩余肾脏的肾小管工作量而增强了线粒体生物能。数据表明线粒体成为UNX后ROS增加的主要来源，并且可能代表重要的肥大信号传导机制。