血管内皮生长因子可加速实验性血栓性微血管病中的肾脏恢复。

Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy.

作者信息

Kim Y G, Suga S I, Kang D H, Jefferson J A, Mazzali M, Gordon K L, Matsui K, Breiteneder-Geleff S, Shankland S J, Hughes J, Kerjaschki D, Schreiner G F, Johnson R J

机构信息

Division of Nephrology, University of Washington Medical Center, Seattle, Washington, USA.

出版信息

Kidney Int. 2000 Dec;58(6):2390-9. doi: 10.1046/j.1523-1755.2000.00422.x.

DOI:10.1046/j.1523-1755.2000.00422.x

PMID:11115072

Abstract

BACKGROUND

Renal microvascular injury characterizes thrombotic microangiopathy (TMA). The possibility that angiogenic growth factors may accelerate recovery in TMA has not been studied.

METHODS

TMA was induced in rats by the selective right renal artery perfusion of antiglomerular endothelial cell IgG (30 mg/kg). Twenty-four hours later, rats received vascular endothelial growth factor (VEGF121, 100 microg/kg/day) or vehicle (control) daily until day 14. To evaluate renal function, the unperfused left kidney was removed at day 14, and rats were sacrificed at day 17.

RESULTS

The induction of TMA was associated with loss of glomerular and peritubular capillary endothelial cells and decreased arteriolar density at day 1. Some spontaneous capillary recovery was present by day 17; however, repair was incomplete, and severe tubulointerstitial damage occurred. The lack of complete microvascular recovery was associated with reduced VEGF immunostaining in the outer medulla. VEGF-treated rats had more glomeruli with intact endothelium, less glomerular ischemia (collapsed glomeruli), and greater peritubular capillary density with less peritubular capillary loss. This was associated with less tubulointerstitial fibrosis, less cortical atrophy, and improved renal function.

CONCLUSIONS

VEGF accelerates renal recovery in this experimental model of TMA. These studies suggest that angiogenic growth factors may provide a new therapeutic strategy for diseases associated with endothelial cell injury.

摘要

背景

肾微血管损伤是血栓性微血管病（TMA）的特征。血管生成生长因子是否能加速TMA的恢复尚未得到研究。

方法

通过选择性右肾动脉灌注抗肾小球内皮细胞IgG（30mg/kg）诱导大鼠发生TMA。24小时后，大鼠每天接受血管内皮生长因子（VEGF121，100μg/kg/天）或赋形剂（对照），直至第14天。为评估肾功能，在第14天切除未灌注的左肾，并在第17天处死大鼠。

结果

TMA的诱导与第1天肾小球和肾小管周围毛细血管内皮细胞的丧失以及小动脉密度降低有关。到第17天出现了一些自发性毛细血管恢复；然而，修复并不完全，并且发生了严重的肾小管间质损伤。微血管恢复不完全与外髓质中VEGF免疫染色减少有关。接受VEGF治疗的大鼠有更多内皮完整的肾小球，肾小球缺血（塌陷肾小球）较少，肾小管周围毛细血管密度更高，肾小管周围毛细血管损失较少。这与较少的肾小管间质纤维化、较少的皮质萎缩和改善的肾功能有关。