Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Am J Pathol. 2011 Apr;178(4):1891-8. doi: 10.1016/j.ajpath.2010.12.029. Epub 2011 Mar 3.
Chronic kidney disease is characterized by progressive glomerulosclerosis and tubulointerstitial fibrosis. High-dose angiotensin type 1 receptor blocker (ARB) or angiotensin-converting enzyme inhibitor can induce regression of existing glomerulosclerosis, at least in part by decreasing matrix accumulation. However, the potential mechanisms of remodeling of capillary loops remain obscure. This study aimed to determine whether capillary branching was augmented in glomeruli with ARB-induced regression of sclerosis. Three-dimensional confocal images were assessed by graph theory analysis to explore the topology of the glomerular capillary network. Compared with normal glomeruli, glomeruli of rats with progressive sclerosis were enlarged but had a significantly reduced number of capillary segments and capillary branch points and decreased complexity of the glomerular network. In contrast, in rats with regression of sclerosis induced by ARB, glomerular enlargement was due to a significantly increased number of glomerular capillary segments and capillary branch points and restored complexity of the capillary network. These data support the theory that capillary growth contributes to regression of sclerosis and is mediated at least in part by ARB-induced increased complexity and branching of capillary segments.
慢性肾脏病的特征是进行性肾小球硬化和肾小管间质纤维化。高剂量血管紧张素受体阻滞剂（ARB）或血管紧张素转换酶抑制剂可诱导已存在的肾小球硬化消退，至少部分是通过减少基质积聚。然而，毛细血管袢重塑的潜在机制仍不清楚。本研究旨在确定 ARB 诱导的硬化消退是否会增加肾小球中的毛细血管分支。通过图论分析评估三维共聚焦图像，以探讨肾小球毛细血管网络的拓扑结构。与正常肾小球相比，进行性硬化大鼠的肾小球增大，但毛细血管节段和毛细血管分支点数量明显减少，肾小球网络的复杂性降低。相比之下，在 ARB 诱导的硬化消退大鼠中，肾小球增大是由于肾小球毛细血管节段和毛细血管分支点数量显著增加以及毛细血管网络的复杂性恢复所致。这些数据支持这样一种理论，即毛细血管生长有助于硬化消退，至少部分是由 ARB 诱导的毛细血管节段复杂性和分支增加介导的。
