Gazzard Sarah E, Cullen-McEwen Luise A, Nikulina Marina, Clever Arnold B, Gardiner Bruce S, Smith David W, Lee Chang-Joon, Nyengaard Jens R, Evans Roger G, Bertram John F
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Anat Rec (Hoboken). 2025 May;308(5):1492-1503. doi: 10.1002/ar.25576. Epub 2024 Sep 5.
Fibrosis and loss of functional capillary surface area may contribute to renal tissue hypoxia in a range of kidney diseases. However, there is limited quantitative information on the impact of kidney disease on the barriers to oxygen diffusion from cortical peritubular capillaries (PTCs) to kidney epithelial tubules. Here, we used stereological methods to quantify changes in total cortical PTC length and surface area, PTC length and surface densities, and diffusion distances between PTCs and kidney tubules in adenine-induced kidney injury. After 7 days of oral gavage of adenine (100 mg), plasma creatinine was 3.5-fold greater than in vehicle-treated rats, while total kidney weight was 83% greater. The total length of PTCs was similar in adenine-treated (1.47 ± 0.23 km (mean ± standard deviation)) to vehicle-treated (1.24 ± 0.24 km) rats, as was the surface density of PTCs (0.025 ± 0.002 vs. 0.024 ± 0.004 μm/μm). The total surface area of PTCs was 69% greater in adenine-treated than vehicle-treated rats. However, the length density of PTCs was 28% less in adenine-treated than vehicle-treated rats. Diffusion distances, from PTCs to the basal membrane of the nearest renal tubule (108%), and to the mid-point of the cytoplasmic height of the nearest tubular epithelial cell (57%), were markedly increased. These findings indicate that, in adenine-induced kidney injury, expansion of the renal cortical interstitium increases the distance required for diffusion of oxygen from PTCs to tubules, rendering the kidney cortex susceptible to hypoxia.
在一系列肾脏疾病中，纤维化和功能性毛细血管表面积的丧失可能导致肾组织缺氧。然而，关于肾脏疾病对氧气从皮质肾小管周围毛细血管（PTCs）扩散到肾上皮小管的屏障的影响，定量信息有限。在这里，我们使用体视学方法来量化腺嘌呤诱导的肾损伤中皮质PTCs的总长度和表面积、PTCs的长度和表面密度以及PTCs与肾小管之间的扩散距离的变化。在口服腺嘌呤（100mg）7天后，血浆肌酐比载体处理的大鼠高3.5倍，而肾脏总重量高83%。腺嘌呤处理的大鼠（1.47±0.23km（平均值±标准差））与载体处理的大鼠（1.24±0.24km）的PTCs总长度相似，PTCs的表面密度也相似（0.025±0.002对0.024±0.004μm/μm）。腺嘌呤处理的大鼠的PTCs总表面积比载体处理的大鼠大69%。然而，腺嘌呤处理的大鼠的PTCs长度密度比载体处理的大鼠低28%。从PTCs到最近肾小管基底膜的扩散距离（108%）以及到最近肾小管上皮细胞胞质高度中点的扩散距离（57%）显著增加。这些发现表明，在腺嘌呤诱导的肾损伤中，肾皮质间质的扩张增加了氧气从PTCs扩散到肾小管所需的距离，使肾皮质易受缺氧影响。
