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Hypoperfusion of Peritubular Capillaries Induces Chronic Hypoxia before Progression of Tubulointerstitial Injury in a Progressive Model of Rat Glomerulonephritis

管周毛细血管 缺氧(环境) 病理 微循环 肾小球肾炎 肾脏疾病 肾血流 肾循环 肾小球 内科学 生物 内分泌学 医学 化学 氧气 有机化学
作者
Makiko Matsumoto,Tetsuhiro Tanaka,Tokunori Yamamoto,Eisei Noiri,Toshio Miyata,Reiko Inagi,Toshiro Fujita,Masaomi Nangaku
出处
期刊:Journal of The American Society of Nephrology 卷期号:15 (6): 1574-1581 被引量:155
标识
DOI:10.1097/01.asn.0000128047.13396.48
摘要

ABSTRACT. Chronic hypoxia likely plays a pivotal role in chronic renal disease, but the specifics of its involvement remain unclear. To elucidate how chronic hypoxia occurs and whether hypoxia participates in the progression of renal disease, the authors established an irreversible glomerulonephritis model induced by uninephrectomy and repeated anti-Thy-1 antibody injections. Glomerulosclerosis with microvascular obliteration was complete at 2 wk after antibody injection and was not restored until 11 wk. Tubulointerstitial injury was mild at 2 wk and was gradually exacerbated until 11 wk, a pattern that was in accordance with the loss of peritubular capillaries. Immunohistochemical analysis using pimonidazole revealed the augmentation of hypoxia in the cortex before the aggravation of tubulointerstitial injury and subsequent peritubular capillary loss. The preexistence of hypoxia implies that it had substantial participation in the progression of tubulointerstitial injury. To test whether blood flow was inhibited in diseased kidneys, capillaries with intact blood flow were identified by tail vein injection of biotinylated lectin specific to endothelial cells. The renal microvasculature was well recognized by lectin in the controls, whereas lectin binding to peritubular capillaries was strikingly decreased in diseased kidneys, suggesting a disturbance of blood flow. Intravital microscopy analysis confirmed that blood flow in peritubular capillaries was decreased by approximately 40% in the disease group compared with the controls. In conclusion, stagnation of blood flow in peritubular capillaries induced chronic hypoxia at an early stage in this model, which was followed by progressive tubulointerstitial injury and a loss of peritubular capillaries.

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