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.

Keywords

septic shock / lipopolysaccharide / urokinase-type plasminogen activator / plasminogen activator inhibitor-1 / simvastatin

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