Netrin-1 Attenuates the Progression of Renal Dysfunction by Inhibiting Peritubular Capillary Loss and Hypoxia in 5/6 Nephrectomized RatsCao N.a,b · Feng J.a · Bai J.b · Sun L.a · Li S.a · Ma J.a · Wang L.a
aDepartment of Nephrology, First Affiliated Hospital of China Medical University, Shenyang, and bDepartment of blood purification, General Hospital of Shenyang Military Area Command, Shenyang, China
Department of Nephrology, First Affiliated Hospital of China Medical University
155 North Nanjing Street, Shenyang City, Liaoning Province 110001 (PR China)
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Background/Aims: The aim of this study was to investigate the effect of netrin-1 on peritubular capillary (PTC) loss and hypoxia in 5/6 nephrectomized (Nx) rats. Methods: Male Sprague-Dawley rats were divided into three groups (n = 10 rats/group): sham-operated rats treated with control adenovirus; 5/6 Nx rats treated with control adenovirus; and 5/6 Nx rats treated with recombinant adenovirus mediated netrin-1 gene (Ad-netrin-1) therapy. Rats were killed 12 weeks after surgery. Blood urea nitrogen (BUN), serum creatinine (Scr) and 24-h urinary albumin excretion rates were measured. Pathological changes in renal tissues were analyzed histologically. The concentration of netrin-1, CD34, and hypoxia-inducible factor-1α (HIF-1α) were analyzed by immunohistochemistry, Western blotting and real-time PCR. Results: Renal function and histopathological damage were significantly improved in Adnetrin-1 treated 5/6 Nx rats, compared with rats treated with the control adenovirus in the 5/6 Nx group. Furthermore, Ad-netrin-1 treatment induced a significant increase in renal PTC density, accompanied by a significant decrease in HIF-1α expression. Conclusion: Adenovirus mediated netrin-1 treatment attenuates PTC damage, relieves tissues hypoxia and improves renal function, thus alleviating renal pathological changes and interstitial fibrosis in 5/6 Nx rats.
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