Ultrastructure of tubular epithelial cells in response to microembolism-induced chronic ischemic injury in rats
Ultrastructure of tubular epithelial cells in response to microembolism-induced chronic ischemic injury in rats
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DOI：
10.1159/000074841
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发表时间：
2003-01-01
影响因子：
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通讯作者：
Hishida, A
中科院分区：
文献类型：
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作者：
Fujigaki, Y;Kimura, M;Hishida, A
背景资料：近端肾小管上皮细胞（PTEC）极化丧失伴脱落是急性肾小管坏死期间PTEC对急性缺血的早期反应。然而，慢性缺血损伤后早期PTECs的形态学变化尚不清楚。我们以前报道过大鼠肾微栓塞引起慢性肾小管间质缺血和广泛的近端肾小管萎缩。在萎缩的肾小管中，有些肾小管表现出与完整的和萎缩的上皮细胞混合的特殊模式，这被认为是导致萎缩的肾小管的最早特征。方法：切除大鼠右肾，左肾灌注微球，造成慢性缺血性损伤。电镜观察4、8、12周后肾小管超微结构的变化，尤其是肾小管萎缩的过程。结果：PTECs的早期变化表现为基底外侧内折和微绒毛的丢失或减少等轻度的简化或去分化。适度简化的PTECs部分脱离肾小管基底膜（TBM），在分离的空间中产生基质，但保持PTECs之间的细胞-细胞接触。在晚期，严重简化的PTECs显示完全脱离TBM和更多的萎缩特征，其特征在于鹅卵石外观与细胞之间的均匀附着。与这些PTEC变化一致，首先在间质间隙中发现间质成纤维细胞样细胞（FLC）与胶原基质的积累，然后在PTEC与TBM分离的空间中发现。结论：我们的研究结果表明，微栓塞诱导的慢性缺血性损伤诱导PTEC去分化和脱离与FLC激活音乐会与基质生产的TBM，导致肾小管间质损伤的特点是肾小管萎缩和肾纤维化。版权所有（C）2003 S. Karger AG，巴塞尔。
Background: Loss of polarization of proximal tubular epithelial cells (PTECs) with detachment is known as an early response of PTEC to acute ischemia during acute tubular necrosis. However, the early morphologic changes of PTECs to chronic ischemic injury are not clear. We previously reported that rat renal microembolism induced chronic tubulointerstitial ischemia and extensive proximal tubular atrophy. Among atrophic tubules, some tubules showed a peculiar pattern mixed with intact and atrophic epithelial cells, which was thought to be the earliest feature leading to atrophic tubules. Methods: Chronic ischemic injury was induced by the left renal perfusion of microspheres after removal of the right kidney in rats. The ultrastructual changes, especially focusing on the process of tubular atrophy, are examined by electron microscopy after 4, 8 and 12 weeks. Results: Early changes in PTECs showed slight simplification or dedifferentiation such as loss or diminution of basolateral infolding and microvilli. Moderately simplified PTECs were partially detached from the tubular basement membrane (TBM) with matrix production in the detached spaces but maintained cell-cell contacts between PTECs. In the advanced stage, severely simplified PTECs showed complete detachment from TBM and more atrophic features characterized by cobblestone appearance with a uniform attachment between cells. In concert with these PTEC changes, accumulation of interstitial fibroblast-like cells (FLCs) with collagenous matrices could be found first in the interstitial spaces and later in the spaces where PTECs detached from TBM. Conclusion: Our results suggest that microembolism-induced chronic ischemic injury induces PTEC dedifferentiation and detachment from TBM with matrix production in concert with FLC activation, resulting in tubulointerstitial damage characterized by tubular atrophy and renal fibrosis. Copyright (C) 2003 S. Karger AG, Basel.