Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II. Exogenous VEGF
Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II. Exogenous VEGF
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DOI：
10.1152/ajprenal.00294.2005
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Chevalier, Robert L.
中科院分区：
文献类型：
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作者：
Burt, Laura E.;Forbes, Michael S.;Chevalier, Robert L.
新生大鼠慢性单侧输尿管梗阻（UUO）可导致肾成熟延迟、肾小管细胞凋亡和间质炎症。血管内皮生长因子（VEGF）作为肾小管细胞的存活因子，在几种肾脏疾病模型中减少肾损伤。为了确定外源性VEGF是否减轻UUO引起的肾损伤，在出生后48小时内对大鼠进行假手术、部分UUO或完全UUO。每天两次注射盐水载体或VEGF（121）（50 mg/kg），持续7天，之后收获肾脏用于组织学研究。血小板-内皮细胞粘附分子-1免疫组化染色检测肾小管周围毛细血管密度，增殖细胞核抗原染色检测增殖细胞核，转移酶介导的dUTP缺口末端标记技术检测凋亡，艾德-1免疫组化染色检测巨噬细胞，天狼星红染色检测胶原。测定各组大鼠肾小球数目和成熟指数。新生大鼠慢性完全UUO后，肾小管周围毛细血管密度显著降低。皮质毛细血管密度进一步降低外源性VEGF在部分梗阻的肾脏。虽然UUO也减少肾小球数量和延迟肾小球成熟，外源性VEGF没有产生额外的影响。细胞增殖和肾小管凋亡的增加与梗阻的严重程度成比例，但外源性VEGF对增殖，肾小管凋亡或巨噬细胞浸润没有额外的影响。然而，VEGF减少了部分UUO肾间质细胞凋亡。我们的结论是，血管内皮生长因子并没有有益的影响所造成的慢性UUO在新生大鼠的肾脏病变，实际上可能会恶化梗阻性肾病加重间质病变。
Chronic unilateral ureteral obstruction (UUO) in the neonatal rat causes delayed renal maturation, tubular apoptosis, and interstitial inflammation. Vascular endothelial growth factor (VEGF) acts as a survival factor for tubular cells and reduces renal injury in several models of renal disease. To determine whether exogenous VEGF attenuates renal injury from UUO, rats were subjected within the first 48 h of life to sham operation, partial UUO, or complete UUO. Saline vehicle or VEGF(121) (50 mg/kg) was injected twice daily for 7 days, after which kidneys were harvested for histological study. The density of peritubular capillaries was measured with platelet-endothelial cell adhesion molecule-1 immunostaining, proliferating nuclei were detected by proliferating-cell nuclear antigen staining, apoptosis by the transferase-mediated dUTP nick end-labeling technique, macrophages by ED-1 immunostaining, and collagen by Sirius red staining. Glomerular number and maturation index were also determined in each group. Following chronic complete UUO in the neonatal rat, peritubular capillary density was significantly decreased. Cortical capillary density was further reduced by exogenous VEGF in the partially obstructed kidney. While UUO also decreased glomerular number and delayed glomerular maturation, exogenous VEGF exerted no additional effects. Cellular proliferation and tubular apoptosis increased in proportion to the severity of obstruction, but exogenous VEGF had no additional effects on proliferation, tubular apoptosis, or macrophage infiltration. However, VEGF reduced interstitial apoptosis in the kidney with partial UUO. We conclude that VEGF does not have salutary effects on the renal lesions caused by chronic UUO in the neonatal rat and may actually worsen obstructive nephropathy by aggravating the interstitial lesions.