高游离脂肪酸引起肺损伤的大鼠模型的建立

摘要

目的:观察血游离脂肪酸(free fatty acids,FFA)升高对肺组织的损伤及辛伐他汀对此类肺损伤的保护作用.方法:将56只成年雄性SD大鼠随机分为4组,每组14只.4组分别为对照组(不予处理)、高三酰甘油血症组(HTG组)、高游离脂肪酸组(FFA组)、他汀组(实验前给予辛伐他汀,建立高游离脂肪酸模型同FFA组).4组动物模型建立后各取8只采集其血和肺组织,检测血脂(总胆固醇、三酰甘油、FFA)、脂质过氧化指标[丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、血细胞因子[白细胞介素-6(interleukin-6,IL-6),肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),内皮素-1(endothelin-1,ET-1),细胞黏附分子-1(intercellular adhesion module-1,ICAM-1)],并进行动脉血气分析和肺组织病理检查.4组各选取6只大鼠进行伊文思蓝试验,测定肺血管通透性.结果:HTG组、FFA组和他汀组血脂指标均较对照组显著升高,FFA组FFA比HTG组升高2倍以上.FFA组肺损伤明显,表现为血氧分压下降、肺毛细血管通透性升高、肺间质增厚和炎症细胞浸润、肺毛细血管淤血；同时MDA升高,SOD降低,ID6、TNF-α、ET-1和ICAM-1均显著升高.HTG组肺损伤程度较轻,该组除ET-1外,各过氧化指标和细胞因子水平改变均较FFA组小.他汀组血脂水平低于FFA组,血氧、病理、血管通透性、过氧化指标和细胞因子均较FFA组有改善.结论:血FFA升高可能通过脂质过氧化途径和ICAM-1途径引起肺损伤,辛伐他汀对此有保护作用.%Objective:To build a rat model of lung injury induced by high level of free fatty acids (FFA),and to investigate the protective effect of Simvastatin. Methods: A total of 56 male adult Sprague-Dawley rats were divided into four groups: the control group,HTG group (hypertriglyceridemia model),FFA group (high FFA model) and Statin group (rats were treated with simvastatin before they were injected with high FFA). After the models were set up,eight rats in each group were anesthetized and blood samples and lung tissues were collected. Six rats in each group underwent Evans blue test for pulmonary capillary permeability. Arterial blood gas,serum lipid (total cholesterol,triglyceridel,FFA),peroxidation index[malondialdehyde (MDA),superoxide dismutase(SOD) ]and cytokines [interleukin-6( IL-6),tumor necrosis factor-α (TNF-α),endothelin-1 (ET-1),intercellular adhesion module-l( ICAM-1)] were tested. Pathologic changes of the lungs were observed. Results; Serum lipid in HTG group,FFA group and Statin group were all elevated compared to the control group,and FFA in FFA group was about double of that in HTG group. In FFA group lung injury was obvious,including dropped blood oxygen,increased pulmonary capillary permeability,pulmonary interstitial thickening,inflammatory cell infiltration,and pulmonary capillary congestion,accompanied with MDA augmentation,decrease of SOD,and increase of IL-6,TNF-α,ET-1,ICAM-1. Lung injury in HTG group were less serious than FFA group. The Statin group showed lower serum lipid than FFA group,and blood oxygen,pathologic changes,pulmonary capillary permeability,lipid peroxidation index and cytokine in statin group was ameliorated. Conclusions: High level of FFA can induce lung injury through lipid peroxidation and ICAM-1 pathway in rat model. Simvastatin can reduce lung injury in this model.