Peritubular capillary network in 5/6 nephrectomized rats undergoing naked netrin-1 plasmid transfection / 中国组织工程研究

ABSTRACT

BACKGROUND:Renal tubular-interstitial lesion and fibrosis induced by peritubular capil ary reduction is a common pathway for various chronic kidney diseases which eventual y develop into end-stage renal failure. How to increase the density of peritubular capil ary network is the key to resolving renal interstitial fibrosis. Netrin-1, as a potent mitogen of vascular endothelial cel s, can promote the migration and proliferation of vascular endothelial cel s and induce angiogenesis. OBJECTIVE:To observe the protective effects of naked netrin-1 plasmid transfer on the remnant renal function of 5/6 nephrectomized rats and the effects of naked netrin-1 plasmid transfer on peritubular capil ary network, and to further discuss the possible mechanism. METHODS:Thirty Sprague-Dawley rats were randomly divided into sham, model and treatment groups. Upper and lower one-third of the rat left kidney was resected in the model and treatment groups, and then the right kidney was resected after 1 week to prepare remnant kidney models in rats. IRES2-EGFP and pCMV6-XL5-Netrin-1-IRES2-EGFP pGenesil-NPs plasmids were intravenously injected into the left renal vein while resecting the right kidney of rats in the model and treatment groups, respectively. RESULTS AND CONCLUSION:Compared with model group, the levels of blood urea nitrogen and serum creatinine decreased, the degree of renal interstitial fibrosis al eviated, the density of peritubular capil aries increased, and the netrin-1 protein expression in renal tubular cytoplasm increased in the treatment group. These findings suggest that the naked netrin-1 plasmid transfer can significantly improve the renal function of the 5/6 nephrectomized rats, reduce the pathological lesion and renal interstitial fibrosis of the remnant kidney, increase the density of peritubular capil aries, and decrease the expression of hypoxia-inducible factor 1α, thereby improving the anoxic condition of renal interstitial tubules.