摘要
目的研究腹腔注射内毒素(LPS)和(或)静脉注射油酸(OA)的方法致大鼠急性肺损伤(ALI)模型的不同特点及其可能机制。方法将24只雄性Wistar大鼠随机分为4组,每组6只。对照组(C组):腹腔注射生理盐水10ml/kg;内毒素组(LPS组):腹腔注射1%LPS10mg/kg;油酸组(OA组):静脉注射OA0.15ml/kg;内毒素+油酸组(LPS+OA组):腹腔注射1%LPS10mg/kg,30min后静脉注射OA0.15ml/kg。观察120min内各组大鼠平均动脉压和心率变化率的改变。120min后处死动物采集标本。分别检测肺组织核转录因子κB(NF-κB)P65、血清IL-6、肺组织髓过氧化物酶(MPO)含量、动脉血气指标和肺组织湿-干重比(W/D),HE染色观察肺组织病理学改变。结果与C组比较,LPS组肺组织NF-κBp65水平、MPO含量及血清IL-6含量显著增加,肺组织W/D比值及血气分析结果无显著性差异,病理组织学改变轻微;OA组肺组织NF-κBp65水平和MPO含量及血清IL-6含量无显著改变,肺组织W/D比值升高,pH值和PaO2降低,PaCO2升高,肺脏出现严重的肺泡上皮细胞损伤和肺泡结构破坏。LPS+OA组肺组织NF-κBp65水平、MPO含量和W/D比值及血清IL-6含量显著增加,pH值和PaO2降低,PaCO2升高,肺泡破坏严重,大量组织液渗出。结论内毒素复合油酸可以产生协同作用,产生大量致炎细胞因子,并造成大鼠严重的肺脏病理生理改变,临床ALI/ARDS发病过程更为接近,是一种研究ALI发病机制及早期干预的较理想的动物模型。
Objective To compare the characteristics of the animal models of acute lung injury induced by oleic acid(OA) and(or) lipopolysaccharide (LPS) in rats.Methods Twenty four male Wistar rats were randomly divided into four groups(n=6):control group (no interventions), group administered LPS only (10 mg/kg, intraperitoneally), group administered OA only (0.15 ml/kg, intravenously), and group administered LPS+OA (OA given 30 minutes after LPS).The mean arterial blood pressure (MAP) and heart rate (HR) were monitored continuously.Blood and tissue samples were collected 120 minutes after the first drug injection.The NF-κB p65, MPO of lung tissue and serum IL-6 were measured respectively.The blood gas analysis, wet to dry ratio (W/D) of right lung and pathological changes were also observed.Results As compared with the control group, the expression of NF-κB p65 and the activity of MPO in lung tissue and serum IL-6 levels were increased in the LPS group, but the W/D ratio and gas exchange were no statistically significant.In contrast, OA caused severe alveolar damage with associated abnormalities in gas exchange and the W/D ratio, but the expression of NF-κB p65 and the activity of MPO in lung tissue and serum IL-6 levels had no change.When given together, LPS and OA acted synergistically to increase the expression of NF-κB p65 and MPO activity in lung tissue and serum IL-6 levels, the W/D ratio and PaCO2 significantly increased and pH and PaO2 markedly decreased.The histopathologic changes of lung tissue showed alveolar hemorrhage, necrosis and proteinaceous alveolar edema.Conclusions "Two-hit" model of acute lung injury induced by oleic acid combined with lipopolysaccharide is an ideal model for ALI, which mimics clinical manifestations.
出处
《北京医学》
CAS
2010年第8期637-640,共4页
Beijing Medical Journal
关键词
急性肺损伤
动物模型
内毒素
油酸
Acute lung injury Animal model Lipopolysaccharide Oleic acid