Simvastatin Suppresses Lung Inflammatory Response in a Rat Cardiopulmonary Bypass Model

Abstract

Inflammatory response in the lungs is a well-known complication after cardiopulmonary bypass (CPB). The main aims of our study were to explore whether pretreatment with simvastatin would inhibit toll-like receptor 4 expression and suppress lung inflammatory response in a rat CPB model. Male Sprague-Dawley rats were divided into four groups (n = 6 each): sham group; CPB (control group); CPB plus low-dose simvastatin (5 mg/kg daily [L-Sim group]); and CPB plus high-dose simvastatin (10 mg/kg daily [H-Sim group]). Blood samples were collected at the beginning and at the termination of CPB, and at 1, 2, 4, and 24 hours after operation. The bronchoalveolar lavage fluid and lungs were harvested 24 hours postoperatively. The simvastatin-treated groups had significantly higher ratios of PaO(2)/FiO(2) and lower values of respiratory index than the control group. We observed that simvastatin reduced CPB-induced toll-like receptor 4 and nuclear factor-kappaB expressions in CPB groups (p < 0.01, versus control group). The levels of interleukin-6, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 in serum, bronchoalveolar lavage fluid, and lung tissues increased in CPB groups, whereas pretreatment with simvastatins reduced these inflammatory marks in a dose-dependent manner (p < 0.01, versus control group). Furthermore, pretreatment with simvastatin had a lower lung injury score (p < 0.05, versus control group). These findings suggest that simvastatin inhibited CPB-induced toll-like receptor 4 upregulation and nuclear factor-kappaB activation, efficaciously reduing the pulmonary inflammatory response after CPB.