Decompression of Inflammatory Edema Along With Endothelial Cell Therapy Expedites Regeneration After Renal Ischemia-Reperfusion Injury
Decompression of Inflammatory Edema Along With Endothelial Cell Therapy Expedites Regeneration After Renal Ischemia-Reperfusion Injury
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DOI：
10.3727/096368912x658700
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Guba, Markus
中科院分区：
文献类型：
--
作者：
Herrler, Tanja;Wang, Hao;Guba, Markus
由于缺血后水肿引起的压力增加加重了肾缺血再灌注损伤（IRI）。采用微囊切开术的预防性手术减压可改善IRI后的肾功能障碍。支持性细胞疗法联合微囊切开术可能协同保护肾功能对抗IRI。在异种小鼠45分钟热肾缺血模型中研究了单独应用治疗性内皮细胞和联合微囊切开术的效果。分别于缺血前、缺血后第2天和第18天用Tc-99 m-MAG_3显像和激光多普勒测定肾功能和血流灌注。组织学分析包括内皮标志物MECA-32、细胞增殖标志物Ki-67和巨噬细胞标志物F4/80的H&E染色和免疫组织学。使用肾小管损伤评分量化组织形态学变化。缺血45分钟导致严重的组织损伤和肾功能和灌注的显着下降。单独的微囊切开术和细胞治疗对肾功能没有显著影响，而只有手术减压显著增加了缺血肾脏的血流量。然而，微囊切开术和细胞疗法的组合显著改善了肾功能和灌注。如通过肾小管损伤评分和MECA-32染色所确定的，组合疗法显著减少缺血性肾的形态学损伤。通过F4/80染色证明的巨噬细胞浸润显著减少。Ki-67增殖指数增加，提示再生环境。虽然微囊切开术和细胞治疗单独对IRI后的肾恢复作用有限，但联合治疗显示出肾功能、灌注和结构损伤的协同改善。微囊切开术可以为细胞治疗创造一个允许的环境。
Increased pressure due to postischemic edema aggravates renal ischemia-reperfusion injury (IRI). Prophylactic surgical decompression using microcapsulotomy improves kidney dysfunction after IRI. Supportive cell therapy in combination with microcapsulotomy might act synergistically protecting kidney function against IRI. The effects of therapeutic endothelial cell application alone and in combination with microcapsulotomy were investigated in a xenogenic murine model of 45-min warm renal ischemia. Renal function and perfusion were determined before as well as 2 and 18 days postischemia by Tc-99m-MAG3 imaging and laser Doppler. Histological analysis included H&E stains and immunohistology for endothelial marker MECA-32, cell proliferation marker Ki-67, and macrophage marker F4/80. Histomorphological changes were quantified using a tubular injury score. Ischemia of 45 min led to severe tissue damage and a significant decrease in renal function and perfusion. Microcapsulotomy and cell therapy alone had no significant effect on renal function, while only surgical decompression significantly increased blood flow in ischemic kidneys. However, the combination of both microcapsulotomy and cell therapy significantly improved kidney function and perfusion. Combination therapy significantly reduced morphological injury of ischemic kidneys as determined by a tubular injury score and MECA-32 staining. Macrophage infiltration evidenced by F4/80 staining was significantly reduced. The Ki-67 proliferation index was increased, suggesting a regenerative environment. While microcapsulotomy and cell therapy alone have limited effect on renal recovery after IRI, combination therapy showed synergistic improvement of renal function, perfusion, and structural damage. Microcapsulotomy may create a permissive environment for cell therapy to work.