摘要
目的研究乌司他丁在脂多糖(LPS)诱导大鼠急性肺损伤(ALI)时的肺保护作用机制。方法36只健康雄性SD大鼠,随机分为3组:正常对照组(NC组),肺损伤组(LPS组)和乌司他丁治疗组(UTI组),每组12只。复制大鼠ALI模型,LPS组经股静脉缓慢注射LPS 5mg/kg;UTI组在注射LPS后,继续由股静脉注入UTI 50 000U/kg;NC组注入2ml 0.9%氯化钠注射液。各组分别于给药完毕后2、4h测定动脉血氧分压(PaO2),然后经颈动脉放血处死6只动物,收集肺标本测定肺组织湿/干(W/D)质量比值,肺组织匀浆中髓过氧化物酶(MPO)活性、丙二醛(MDA)含量,光镜下检查肺组织病理形态学改变,检测肺组织TNF-α蛋白含量和核转录因子-κB(NF-κB)的表达。结果与NC组比较,LPS组2、4h时的PaO2值均明显下降(P<0.01);UTI组各时间点PaO2均高于LPS组(P<0.05),低于NC组(P<0.05)。UTI组和LPS组之间PaCO2未见明显差异(P>0.05)。UTI组和LPS组肺组织的W/D比值较NC组均有明显增高(P<0.05),但前两者之间并无明显差异(P>0.05)。肺组织病理学检查可见小叶结构紊乱,大量炎性细胞浸润,肺泡腔可见明显出血、渗出,UTI组也存在上述损伤性改变,但程度较LPS组轻。LPS组MPO活性、MDA含量明显高于NC组和UTI组(P<0.05)。LPS组TNF-α蛋白含量、NF-κB表达量均明显高于UTI组(P<0.05)。结论在内毒素诱导ALI时,早期使用UTI能够抑制中性粒细胞和NF-κB活化,减少TNF-α的生成,具有较好的肺保护作用。
Objective To study the mechanism of protective effect of ulinastatin （UTI） on lung with LPS-induced acute lung injury （ALI） in rats. Methods Thirty-six male SD rats were randomly divided into three groups： normal control group （NC）, lipopolysaccharide injury group （LPS） and UTI treatment group （UTI）. ALI model of rats was reproduced with LPS. Rats in LPS group and UTI group received injection of LPS 5mg/kg v/a femoral vein, and then the rats in UTI group received injection of UTI 50 000U/kg. Rats in NC group received an injection of 2ml 0. 9% NaCl. PaO2 was detected for all the three groups 2h and 4h after injection. Half of rats in each group were then sacrificed by exsanguination, and lungs were harvested for the assessment of lung wet/dry weight ratio （W/D）, MPO activity and MDA level. The pathological changes in lung tissues were examined with HE-stained lung sections. TNF-α protein was measured by ELISA, and the expression of NF-κB was examined by immunohistochemistry. Results The W/D ratio of lung tissue was significantly increased in the rats of LPS and UTI group compared with that of NC group （P〈0. 05）, while no significant difference existed between LPS and UTI groups （P〉0. 05）. PaO2 decreased significantly in LPS group at 2h and 4h time points after injection compared with that in NC group （P〈0. 01）. PaOe was higher in UTI group at each time point compared with that in LPS group （P〈0.05）, while lower than that in NC group （P〈0. 05）. No significant difference in PaCO2 was found between UTI and LPS groups （P〉0. 05）. Marked histological damage was found in the lungs of rats of LPS group characterized by destruction of lobules, neutrophil infiltration and hemorrhage in alveolar spaces. Similar changes were also found but in a mild degree in the rats of UTI group. MPO activity and MDA level were significantly higher in LPS group than that in NC and UTI group （P〉0. 05）. The expressions of NF-κB and TNF-α were down regulated in UTI group c
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2009年第5期550-553,共4页
Medical Journal of Chinese People's Liberation Army
