Development of a photoacoustic microscopy technique to assess peritubular capillary function and oxygen metabolism in the mouse kidney
Development of a photoacoustic microscopy technique to assess peritubular capillary function and oxygen metabolism in the mouse kidney
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开发光声显微镜技术评估小鼠肾脏管周毛细血管功能和氧代谢
DOI：
10.1016/j.kint.2021.06.018
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发表时间：
2021
影响因子：
19.6
通讯作者：
Hu, Song
中科院分区：
文献类型：
--
作者：
Sun, Naidi;Zheng, Shuqiu;Rosin, Diane L.;Poudel, Nabin;Yao, Junlan;Perry, Heather M.;Cao, Rui;Okusa, Mark D.;Hu, Song
长期以来，微循环变化和氧化应激与急性肾损伤相关。尽管双光子显微镜在啮齿动物模型中对急性肾损伤的微血管反应方面取得了实质性进展，但对血氧输送和组织氧代谢的潜在变化知之甚少。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体内肾小管周围毛细血管中的血红蛋白浓度、血红蛋白的氧饱和度和血流。基于这些微血管参数，微区域氧代谢进行了量化。我们通过研究脂多糖诱导的脓毒症小鼠急性肾损伤时的肾脏血流动力学和氧代谢反应，证明了该技术的实用性。动态光声显微镜的管周毛细血管功能和组织氧代谢显示，脓毒症引起的急性和显着减少管周毛细血管氧饱和度的血红蛋白，伴随着显着减少肾脏ATP水平和对比的名义变化管周毛细血管流量和血浆肌酐。因此，我们的技术为研究急性和慢性肾脏疾病的微血管和代谢功能障碍提供了新的机会。
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 capillariesin 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.