Abstract
We investigated the effects of RNAi-mediated gene silencing of vascular endothelial growth factor (VEGF) on ultrafiltration failure (UFF) in rats with peritoneal dialysis (PD). Sprague–Dawley (SD) male rats were classified into normal, sham operation, and uremic model groups. Uremic rats were subcategorized into uremia, PD2, VEGF shRNA-2, vector-2, PD2 + Endostar, PD4, VEGF shRNA-4, Vector-4, and PD4 + Endostar groups. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG). mRNA and protein expressions of VEGF were detected using quantitative real-time PCR (qRT-PCR) and Western blotting. Immunohistochemistry was performed to detect microvessel density (MVD). Compared with the normal group, decreased UFV and increased MTG were observed in rest of the groups. Compared with the uremia group, UFV decreased, while MTG, expression of VEGFs, and number of new blood capillaries increased in the PD2, Vector-2, PD4, and Vector-4 groups. The PD4 and Vector-4 groups exhibited lower UFV and higher MTG than the PD2 group. In the VEGF shRNA-2, PD2 + Endostar, VEGF shRNA-4, and in PD4 + Endostar group increased UFV, reduced MTG and expression of VEGF, and decreased number of new blood capillaries were detected. Compared with the PD4 group, in the VEGF shRNA-4 and PD4 + Endostar groups, UFV increased, MTG and expression of VEGF decreased, and number of new blood capillaries reduced. VEGF expression was negatively correlated with UFV, but positively correlated with MTG. The results obtained in the study revealed that down-regulation of VEGF by RNAi could be a novel target approach for the treatment of UFF.
Highlights
Ultrafiltration failure (UFF) can be understood as the durable loss of ultrafiltration capacity
At the 28th day of Peritoneal dialysis (PD), there was no record of death in rats amongst the normal and sham groups, there were four rats that died from peritonitis in the uremia, PD2, PD4, and vascular endothelial growth factor (VEGF) shRNA-4 groups with one death in each c 2017 The Author(s)
The findings provided by quantitative real-time PCR (qRT-PCR) and Western blotting techniques indicated that, when compared with the normal group, the protein and mRNA expressions of VEGF increased in the peritoneal tissues of rats in the uremia, PD2, Vector-2, PD4, VEGF shRNA-4, Vector-4, and PD4 + Endostar groups
Summary
Ultrafiltration failure (UFF) can be understood as the durable loss of ultrafiltration capacity. This durable loss of capacity is reflected when the daily ultrafiltration volume (UFV) is less than 400 ml [1,2]. There are four widely accepted causes of UFF: high effective peritoneal surface area, low osmotic conductance to glucose, low effective peritoneal surface area, and high total peritoneal fluid loss rate. There are approximately 200000 patients currently suffering from end-stage renal failure and are in need of PD to sustain their life [6]. Approximately 30% patients may suffer UFF following PD treatment for approximately 5 years [7]. UFF largely contributes to the technical failure seen in PD patients [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
