title: A new mouse model of hemorrhagic shock-induced acute kidney injury.
abstract: Current animal models of hemorrhagic shock-induced acute kidney injury (HS-induced AKI) require extensive surgical procedures and constant monitoring of hemodynamic parameters. Application of these HS-induced AKI models in mice to produce consistent kidney injury is challenging. In the present study, we developed a simple and highly reproducible mouse model of HS-induced AKI by combining moderate bleeding and renal pedicle clamping, which was abbreviated as HS-AKI. HS was induced by retroorbital bleeding of 0.4 ml blood in C57BL/6 mice. Mice were left in HS stage for 30 min, followed by renal pedicle clamping for 18 min at 36.8-37.0°C. Mean arterial pressure (MAP) and heart rate were monitored with preimplanted radio transmitters throughout the experiment. The acute response in renal blood flow (RBF) triggered by HS was measured with transonic flow probe. Mice received sham operation; bleeding alone and renal pedicle clamping alone served as respective controls. MAP was reduced from 77 ± 4 to 35 ± 3 mmHg after bleeding. RBF was reduced by 65% in the HS period. Plasma creatinine and kidney injury molecule-1 levels were increased by more than 22-fold 24 h after reperfusion. GFR was declined by 78% of baseline 3 days after reperfusion. Histological examination revealed a moderate-to-severe acute tubular damage, mostly at the cortex-medulla junction area, followed by the medullar and cortex regions. HS alone did not induce significant kidney injury, but synergistically enhanced pedicle clamping-induced AKI. This is a well-controlled, simple, and reliable mouse model of HS-AKI.
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida; leiwang@health.usf.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Song
authors.affiliation: Tampa General Hospital, Tampa, Florida.
authors.forename: Jacentha
authors.initials: J
authors.lastname: Buggs
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.|Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Gensheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi; and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Kay-Pong
authors.initials: KP
authors.lastname: Yip
authors.affiliation: Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D004195:Disease Models, Animal; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000097:blood; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008810:Mice, Inbred C57BL; D012079:Renal Circulation / Q000502:physiology; D012083:Renin / Q000097:blood; D015427:Reperfusion Injury / Q000473:pathology; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology*
chemical_list: C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D012083:Renin
keywords: acute kidney injury; hemorrhagic shock; mice