The Expression Of VEGF And Its Receptors In Chronic Ischemic Renal Disease

Objective:To investigate the role of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2 in chronic ischemia of rat kidney, we studied the expression of them in renal tissue of rats with chronic ischemia. Methods:Chronic ischemia of renal model was induced in male Wistar rats (initial weight, about 25 Og) by clamping the left renal artery incompletely with silver clamp. Blood Pressure and serum creatinine were measured in 1 and 10 weeks respectively. Rats were executed subsequently to obtain renal tissue. Then pathological sections were manufactured and stained, renal tissue was labled with Hypoxyprobe?-1. Immunohistochemical staining and semi-quantitative RT-PCR were used to determine the expression of VEGF and its receptors in chronic ischemia kidney. Results:1. Kidney with its renal artery clamped incompletely showed classic hypoxic change in 1week group: the renal epithelium cells became swelling with granule degeneration, with inflammatory cells infiltrating in some area. 2. Hypoxyprobe?-1 labelling was significant in out medulla and cortex, especially in out medulla. Vascular endothelial growth factor immunohistochemistry staining was similar to that of Hypoxyprobe?-1. The staining and distribution of VEGFR-1 and VEGFR-2 were also significant in the incompletely clamped renal. 3. In 10 weeks group the kidney with its renal artery clamped began to atrophy, and its tubular interstitium widened obviously with severe fibrosis. Hypoxyprobe?-1 staining was still significant in out medulla, cortex staining was negative. Coincidence with Hypoxyprobe?-1, VEGF and its receptors staining in cortex weakened significantly. 4. Vascular endothelialgrowth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2 were measured by semi-quantitative RT-PCR and immunohistochemical staining method. Expression of VEGF and its receptors in 1 week group elevated significantly compared with that in sham group (P < 0.01 ) , and their expression in 10 week reduced significantly compared with sham and 10 week groups (P<0.01).5. Serum creatinine and blood pressure showed no marked change in 1 week group compared with sham group, both elevated significant in 10 week group compared with sham and lweek group.Conclusion:VEGF and its receptors' synthesis and expression in 1 week group elevated significantly compared with sham group that may enhanced angiogenesis ability and compensated for oxygen supply during the early ischemia stage. On the contrary, VEGF and its receptors' synthesis and expression reduced significantly in 10 weeks group with accelerated ischemia of renal and interstitial fibrosis. Although it seemed that the beneficial effects of VEGF on chronic renal disease are attributable to its effects on the receptor of endothelium, it was possible that VEGF could be acting via the receptor of epithelium.