Suppression of glomerular injury by enhancing a VEGF signaling to its endothelial cells

我们研究了血管内皮生长因子对肾小球内皮损伤及其修复的影响。通过向成年Wistar大鼠腹腔注射0.125至0.15μg单克隆抗体（OX7），在大鼠中观察到Thy 1肾小球肾炎（Thy 1 GN）。在注射OX7前4小时和注射后1、2和3天，向大鼠腹膜内注射每剂量10 μg的人重组VEGF 165。分别于注射OX7后24h、4d、18d取肾组织行组织学观察。肾小球系膜，内皮细胞和上皮细胞的变化进行了检查，分别使用抗Thy1，抗vWF和抗PECUM，和抗p250抗体免疫组化。注射OX7后24h，肾小球系膜溶解，毛细血管气球样变，VEGF可抑制后者的发生，使肾小球结构得到明显保护。注射后第4天，VEGF组肾小球损伤修复，系膜细胞和内皮细胞增生，而对照组无修复。18天后，VEGF给药大鼠的肾小球修复几乎完成。在对照组中，观察到系膜增生并进行修复。这些结果表明，重组VEGF 165保护肾小球毛细血管，并促进受损肾小球的修复。残余的毛细血管结构可作为系膜增殖的支架，VEGF对内皮细胞的有丝分裂刺激可促进肾小球修复。虽然还需要进一步的研究，但增强VEGF信号传导可能有助于治疗与内皮损伤相关的人类肾小球肾炎

We studied effects of VEGF on glomerular endothelial injury and its repair. Thy1 glomerulonephritis (Thy1 GN) was * in the rat by intraperitoneal injection of 0.125 to 0.15μg of a monoclonal antibody (OX7) to an adult Wistar rat. Ten μg per dose of human recombinant VEGF165 was injected intraperitoneally to the rat at 4 hours before injecting OX7 and 1, 2 and 3 days after the injection. As a control, BSA was injected instead of the VEGF.Kidneys were harvested at 24hours, 4 days and 18 days after injecting the OX7 and tissues were studied histologically. Changes of glomerular mesangial, endothelial, and epithelial cells were examined by immunohistochemistry using anti-Thy1, anti-vWF and anti-PECUM, and anti-p250 antibodies, respectively. Mitotic changes of the cells were evaluated by staining PCNA.At 24 hours after injecting OX7, mesangiolysis and ballooning of capillaries were observed and VEGF suppressed the latter and significantly preserved the glomerular structure. At 4 days after the injection, a repair of injured glomeruli including proliferations of mesangial and endothelial cells were observed by administrating VEGF.Contrarily, no repair was observed in the control. After 18 days, repair was almost finished in glomeruli of the VEGF-administered rats. In the control, mesangial proliferation was observed and repair was proceeding. These results show that recombinant VEGF165 protects glomerular capillaries and promotes the repair of injured glomeruli. Remained structures of the capillry may be used as a scaffold for mesangial proliferation and a mitotic stimulation of VEGF to endothelial cells may promote the glomerular repair. Although further studies are needed, enhancing VEGF signaling may be useful in the treatment of human glomerulonephritis associated with endothelial injuries