Sun Xiao-feng, Wang Jun-ke, Yang Jun, Zhao Hong
Department of Anesthesiology, Fengtian Hospital, Shenyang Medical College, Shenyang 110024, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1150-3.
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.
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.
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).
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.
探讨辛伐他汀对后肢缺血再灌注（IR）诱导的大鼠肺损伤肺组织中核因子κB（NF-κB）和细胞间黏附分子1（ICAM-1）表达的影响。
将48只成年雄性SD大鼠随机分为6组，每组8只，包括假手术组、IR组、3个IR+辛伐他汀组（分别给予1、5或10 mg·kg⁻¹·d⁻¹辛伐他汀灌胃3天）和辛伐他汀对照组（给予10 mg·kg⁻¹·d⁻¹辛伐他汀）。4个IR组通过阻断双侧股动脉2小时后再灌注3小时诱导后肢IR。再灌注结束时处死大鼠，采集动脉血进行血气分析。立即取出肺组织进行病理检查，并测定肺湿/干重比（W/D）、髓过氧化物酶（MPO）活性和多形核中性粒细胞（PMN）计数。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测肺组织中NF-κB p65 mRNA和ICAM-1蛋白的表达。
IR组可见肺泡水肿、局限性肺不张和大量PMN浸润，3个辛伐他汀组（S(1)、S(5)、S(10)）上述改变有所改善。与假手术组相比，IR组肺W/D、MPO活性和PMN计数显著升高（P<0.01）。与IR组相比，3个辛伐他汀组肺W/D、MPO活性和PMN计数显著降低（P<0.01）。3个辛伐他汀组IR诱导的动脉血氧分压（PaO₂）降低显著升高（P<0.01），且NF-κB p65 mRNA和ICAM-1蛋白表达也呈剂量依赖性显著降低（P<0.01）。
辛伐他汀通过抑制NF-κB激活及随后由ICAM-1介导的中性粒细胞聚集，减轻大鼠后肢IR诱导的肺损伤。
