Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, USA; Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
Kidney Int. 2021 Sep;100(3):613-620. doi: 10.1016/j.kint.2021.06.018. Epub 2021 Jul 2.
Microcirculatory changes and oxidative stress have long been associated with acute kidney injury. Despite substantial progress made by two-photon microscopy of microvascular responses to acute kidney injury in rodent models, little is known about the underlying changes in blood oxygen delivery and tissue oxygen metabolism. To fill this gap, we developed a label-free kidney imaging technique based on photoacoustic microscopy, which enables simultaneous quantification of hemoglobin concentration, oxygen saturation of hemoglobin, and blood flow in peritubular capillaries in vivo. Based on these microvascular parameters, microregional oxygen metabolism was quantified. We demonstrated the utility of this technique by studying kidney hemodynamic and oxygen-metabolic responses to acute kidney injury in mice subject to lipopolysaccharide-induced sepsis. Dynamic photoacoustic microscopy of the peritubular capillary function and tissue oxygen metabolism revealed that sepsis induced an acute and significant reduction in peritubular capillary oxygen saturation of hemoglobin, concomitant with a marked reduction in kidney ATP levels and contrasted with nominal changes in peritubular capillary flow and plasma creatinine. Thus, our technique opens new opportunities to study microvascular and metabolic dysfunction in acute and chronic kidney diseases.
微血管变化和氧化应激一直与急性肾损伤有关。尽管利用双光子显微镜对啮齿动物模型的急性肾损伤的微血管反应进行了大量研究，但对于血液氧输送和组织氧代谢的潜在变化却知之甚少。为了填补这一空白，我们开发了一种基于光声显微镜的无标记肾脏成像技术，该技术能够同时定量测量肾小管周围毛细血管中的血红蛋白浓度、血红蛋白氧饱和度和血流。基于这些微血管参数，对微区氧代谢进行了定量。我们通过研究脂多糖诱导的脓毒症小鼠的急性肾损伤的肾脏血液动力学和氧代谢反应，证明了该技术的实用性。对肾小管周围毛细血管功能和组织氧代谢的动态光声显微镜显示，脓毒症导致肾小管周围毛细血管血红蛋白氧饱和度急性显著下降，同时肾脏 ATP 水平显著降低，而肾小管周围毛细血管流量和血浆肌酐仅有轻微变化。因此，我们的技术为研究急性和慢性肾脏病中的微血管和代谢功能障碍提供了新的机会。
