title: 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.
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.
authors.affiliation: Department of Chemistry, Medical College, Shantou University, Shantou, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tong
authors.affiliation: Department of Chemistry, Medical College, Shantou University, Shantou, People's Republic of China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Chemistry, Medical College, Shantou University, Shantou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry, Medical College, Shantou University, Shantou, People's Republic of China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Chemistry, Medical College, Shantou University, Shantou, People's Republic of China.
authors.forename: Daojun
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D002470:Cell Survival / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use*; D007511:Ischemia / Q000097:blood / Q000473:pathology*; D007668:Kidney / Q000098:blood supply*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008970:Molecular Weight; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D003404:Creatinine; D009195:Peroxidase; D013482:Superoxide Dismutase
keywords: HIF-1α; RI/RILI; VEGF; block copolymer; insulin