Quantitative imaging of basic functions in renal (patho)physiology
Quantitative imaging of basic functions in renal (patho)physiology
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DOI：
10.1152/ajprenal.00521.2005
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Peti-Peterdi, Janos
中科院分区：
文献类型：
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作者：
Kang, Jung Julie;Toma, Ildiko;Peti-Peterdi, Janos
多光子荧光显微镜具有对活组织进行深度光学切片、光毒性最小和光学分辨率高的优点。更重要的是，可以使用非侵入性方法实时可视化完整器官的动态过程和多种功能，并进行量化。这些研究旨在扩展现有的多光子荧光成像方法，以直接观察和量化肾脏的基本生理参数，包括肾小球滤过率（GFR）和渗透性、血流量、尿液浓度/稀释度、肾素含量和释放，以及更综合和复杂的功能，例如肾小球滤过和肾小管血流中肾小球反馈（TGF）介导的振荡。链脲佐菌素诱导的糖尿病使单肾单位 GFR (SNGFR) 从 32.4 +/- 0.4 nl/min 显着增加至 59.5 +/- 2.5 nl/min，肾小球对 70 kDa 荧光团的通透性增加约八倍。袢利尿剂速尿稀释2倍，使远端肾小管液量增加约10倍，同时还导致肾小球旁肾素含量释放20%。与管周血管 (4.7 +/- 0.2 mm/s) 相比，肾小球内毛细血管中单个红细胞的速度 (16.7 +/- 0.4 mm/s) 显着更高。观察到肾小球收缩-舒张的规律周期，导致滤过和肾小管流速的振荡。近端和远端肾小管血流的振荡显示与肾小球滤过相似的周期时间（类似于 45 秒），延迟分别类似于 5-10 秒和 25-30 秒。这些创新技术提供了肾功能最复杂、最直接和动态的描述，清楚地描绘了正常生理学和病理生理学所涉及的组成部分和机制。
Multiphoton fluorescence microscopy offers the advantages of deep optical sectioning of living tissue with minimal phototoxicity and high optical resolution. More importantly, dynamic processes and multiple functions of an intact organ can be visualized in real time using noninvasive methods, and quantified. These studies aimed to extend existing methods of multiphoton fluorescence imaging to directly observe and quantify basic physiological parameters of the kidney including glomerular filtration rate (GFR) and permeability, blood flow, urinary concentration/dilution, renin content and release, as well as more integrated and complex functions like the tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration and tubular flow. Streptozotocin-induced diabetes significantly increased single-nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic furosemide 2-fold diluted and increased similar to 10-fold the volume of distal tubular fluid, while also causing the release of 20% of juxtaglomerular renin content. Significantly higher speeds of individual red blood cells were measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction-relaxation were observed, resulting in oscillations of filtration and tubular flow rate. Oscillations in proximal and distal tubular flow showed similar cycle times (similar to 45 s) to glomerular filtration, with a delay of similar to 5-10 and 25-30 s, respectively. These innovative technologies provide the most complex, immediate, and dynamic portrayal of renal function, clearly depicting the components and mechanisms involved in normal physiology and pathophysiology.