中文摘要：

目的探讨辛伐他汀对肢体缺血再灌注（I/R）肺损伤大鼠肺组织核因子-κB（NF-κB）和细胞间黏附分子-1（ICAM-1）表达的影响及其机制。方法成年雄性SD大鼠48只,体质量250～300g,随机分为6组（n=8）：假手术组（C组）、肢体缺血再灌注组（IR组）分别给予等容量的（1ml）的蒸馏水、辛伐他汀1、5、10mg/（kg·d）组（S1组、S5组、S10组）和辛伐他汀对照组（S组）分别于每日清晨将1、5、10、10mg/（kg·d）辛伐他汀溶于1ml蒸馏水灌胃1次,连续3d,IR组、S1组、S5组和S10组于最后1次给药后2h行肢体缺血再灌注。再灌注3h末行血气分析,观察肺组织病理学变化,测定肺组织湿/干质量比（W/D）、多形核中性粒细胞（PMN）数目、MPO活性、NF-κBp65mRNA及ICAM-1蛋白的表达。结果与C组比较,IR组肺组织病理损伤较重,PaO2降低,W/D、PMN计数和MPO活性升高（P〈0.01）;与IR组相比,S1组、S5组和S10组减轻了肺组织病理损伤,PaO2升高,W/D、PMN计数和MPO活性降低,NF-κBp65mRNA及ICAM-1蛋白表达下调（P〈0.01）。结论辛伐他汀可减轻肢体I/R大鼠的肺损伤,其机制可能与抑制NF-κB激活,从而减少ICAM-1介导的中性粒细胞浸润有关。

英文摘要：

Objective 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.Methods 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.Results 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）.Conclusion 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.