2019 年第 10 期 第 14 卷

富马酸氯马斯汀对大鼠海水淹溺性肺损伤的影响

Effect of clemastine fumarate on seawater drowning induced acute lung injury in rats

作者：山淇周坤陈卓李宏

英文作者：

单位：300162天津，中国人民武装警察部队后勤学院（山淇、陈卓）；300162天津，中国人民武装警察部队特色医学中心麻醉手术一科（周坤、李宏）

英文单位：

关键词：肺损伤；富马酸氯马斯汀；淹溺

英文关键词：

• 摘要：

• 【摘要】目的    探讨富马酸氯马斯汀对大鼠海水淹溺性肺损伤(SW-ALI)的影响。方法    无特定病原体级6周龄雄性SD大鼠36只，按照随机数字表法分为对照组、淹溺组和观察组，每组12只。淹溺组和观察组大鼠麻醉后向气管内注入人工海水4 ml/kg进行SW-ALI制模，随后淹溺组肌内注射0.9%氯化钠注射液，观察组肌内注射富马酸氯马斯汀1 mg/kg。6 h后处死大鼠，摘眼球取血1 ml，酶联免疫吸附试验法检测血浆白细胞介素6(IL-6)、IL-10和肿瘤坏死因子α(TNF-α)含量，干/湿比重法检测肺水肿程度，实时定量荧光聚合酶链反应法检测肺组织中Toll样受体4（TLR4）及核因子κB（NF-κB）mRNA转录水平，蛋白质印迹法检测TLR4及NF-κB蛋白表达水平。结果    与对照组相比，淹溺组和观察组血浆IL-6、IL-10和TNF-α含量均明显升高，肺组织干/湿比重明显降低，肺组织中TLR4和NF-κB的mRNA转录水平［（4.45±0.86）、（3.06±0.52）比（1.02±0.10），（6.71±2.08）、（3.02±1.17）比（1.11±0.28）］及NF-κB蛋白表达水平［（0.72±0.13）、（0.44±0.10）比（0.24±0.05）］均明显升高（均P＜0.05）。与淹溺组相比，观察组IL-6、IL-10和TNF-α含量均明显降低，肺组织干重/湿重明显升高，肺组织中TLR4和NF-κB的mRNA转录水平及蛋白表达水平均明显降低（均P＜0.05）。结论    富马酸氯马斯汀可以减轻大鼠SW-ALI，这可能与氯马斯汀抑制炎性因子及TLR4/NF-κB通路有关。

• 【Abstract】Objective    To explore the effect of clemastine fumarate on seawater drowning induced acute lung injury（SW-ALI） in rats. Methods    Thirty-six male SD rats aged 6 weeks were randomly divided into control group, drowning group and observation group, with 12 rats in each group. The drowning group and observation group were made SW-ALI models by intratracheal injection of artificial sea water 4 ml/kg under anesthesia; the drowning group had intramuscular injection of 0.9% sodium chloride solution; the observation group had intramuscular injection of clemastine fumarate 1 mg/kg. Blood samples were collected from eyeballs after 6 hours; plasma interleukin-6(IL-6), IL-10 and tumor necrosis factor-α(TNF-α) were tested by enzyme linked immunosorbent assay. Pulmonary edema was measured by dry/wet weight ratio of lung tissue. Expressions of Toll-like receptor 4(TLR4) and nuclear factor-κB(NF-κB) mRNA and protein in lung tissue were detected by real-time quantitative fluorescence polymerase chain reaction and western blotting. Results    Compared with the control group, levels of plasma IL-6, IL-10 and TNF-α significantly increased, dry/wet weight ratio of lung tissue significantly decreased; mRNA expression levels of TLR4 and NF-κB significantly increased［（4.45±0.86）,（3.06±0.52） vs （1.02±0.10）, （6.71±2.08）,（3.02±1.17） vs （1.11±0.28）］, protein expression levels of NF-κB significantly increased［（0.72±0.13）,（0.44±0.10） vs （0.24±0.05）］ in the drowning group and observation group(all P＜0.05). Levels of plasma IL-6, IL-10 and TNF-α in the observation group were significantly lower, dry/wet weight ratio of lung tissue was significantly higher, mRNA and protein expression levels of TLR4 and NF-κB were significantly lower than those in the drowning group（all P＜0.05）. Conclusion    Clemastine fumarate can alleviate SW-ALI in rats, which may be related to the inhibition on inflammatory factors and TLR4/NF-κB pathway.