title: Simvastatin prevents lipopolysaccharide-induced septic shock in rats.
abstract: Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis. Herein, we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock. In our study, rats were divided into a saline group, an LPS group and an LPS plus simvastatin group. Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg), with variations in left ventricular pressure recorded throughout. Ninety min after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated from the whole blood using separating medium. The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1). In addition, mesentery microcirculations of inlet diameter, outlet diameter and blood flow rate were measured in all three groups. The results indicated that simvastatin significantly promoted heart systolic function and increased the level of uPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group. Moreover, simvastatin reversed the LPS-induced inhibition of mesentery microcirculation. Taken together, it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.
authors.affiliation: Intensive Care Unit, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China. yuli641006@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xing-Wen
authors.initials: XW
authors.lastname: Da
authors.affiliation: Intensive Care Unit, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ao-di
authors.initials: AD
authors.lastname: He
authors.affiliation: Intensive Care Unit, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Long
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests / Q000187:drug effects; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D019821:Simvastatin; D014568:Urokinase-Type Plasminogen Activator
keywords: lipopolysaccharide; plasminogen activator inhibitor-1; septic shock; simvastatin; urokinase-type plasminogen activator