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The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(L-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

Authors Tong F, Tang X, Li X, Xia W, Liu D

Received 5 November 2015

Accepted for publication 5 February 2016

Published 27 April 2016 Volume 2016:11 Pages 1717—1730

DOI https://doi.org/10.2147/IJN.S99890

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Fei Tong, Xiangyuan Tang, Xin Li, Wenquan Xia, Daojun Liu

Department of Chemistry, Medical College, Shantou University, Shantou, People’s Republic of China

Abstract: The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(L-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine L-glutamate)-g-poly(L-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL) significantly improved this effect.

Keywords: insulin, block copolymer, RI/RILI, HIF-1α, VEGF

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