Effects of simvastatin on pulmonary nuclear factor-κB and intercellular adhesion molecule-1 in rats with lung injury induced by ischemia-reperfusion of the hind limbs / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin on the expression of nuclear factor-κB (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) in the lung tissue of rats with lung injury induced by ischemia-reperfusion (IR) of the hind limbs.</p><p><b>METHODS</b>Forty-eight male adult SD rats were randomized into 6 equal groups, including a sham-operated group, an IR group, 3 IR+simvastatin groups with intragastric administration of 1, 5, or 10 mg·kg(-1)·d(-1) for 3 days, and a simvastatin control group treated with 10 mg·kg(-1)·d(-1) simvastatin. IR of the hind limbs was induced in the 4 IR groups by occlusion of bilateral femoral arteries for 2 h followed by a 3-h reperfusion. The rats were sacrificed at the end of reperfusion and the arterial blood was taken for blood gas analysis. The lungs were immediately removed for pathological examination and determination of the lung Wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity and polymorphonuclear neutrophil (PMN) counting. The expression of NF-κB p65 mRNA and ICAM-1 protein in the lungs was detected using RT-PCR and Western blotting.</p><p><b>RESULTS</b>Alveolar edema, localized pulmonary atelectasis and large amount of PMN infiltration were found in IR group, and these changes were ameliorated in the 3 simvastatin groups (S(1), S(5), S(10)). Lung W/D, MPO activity and PMN counting were significantly increased in IR group as compared with the sham-operated group (P<0.01). Lung W/D, MPO activity and PMN counting were significantly lowered in the 3 simvastatin groups as compared with IR group (P<0.01). IR-induced decrease in PaO(2) was significantly increased in the 3 simvastatin groups (P<0.01), which also showed significantly lowered expressions of NF-κB p65mRNA and ICAM-1 protein in a dose-dependent manner (P<0.01).</p><p><b>CONCLUSION</b>Simvastatin attenuates lung injury induced by IR of the hind limbs in rats by suppressing the activation of NF-κB and subsequent accumulation of neutrophils mediated by ICAM-1.</p>