西维来司钠对烟雾吸入性肺损伤大鼠早期炎症反应的影响

摘要

目的 探讨西维来司钠对大鼠烟雾吸入性肺损伤早期炎症反应的影响.方法 40只健康雄性SD大鼠随机分成正常组、模型组、治疗组,治疗组又分为10、20、30 mg/kg组,每组8只.建立大鼠烟雾吸入性肺损伤模型.治疗组分别给予西维来司钠10、20、30 mg/kg腹腔注射,模型组给予等量生理盐水.24 h后用酶联免疫吸附(ELISA)法检测各组大鼠血清中性粒细胞弹性蛋白酶(NE)、髓过氧化物酶(MPO)、白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α水平,同时测定各组大鼠肺组织含水量,肺组织HE染色后观察,测量比较肺泡间隔厚度.结果 与正常组比较,模型组和治疗组血清中NE、MPO、IL-6、TNF-α水平、肺组织含水量、肺泡间隔厚度均明显升高(均P<0.05);与模型组比较,各治疗组血清NE、MPO、IL-6、TNF-α表达水平、肺组织含水量、肺泡间隔厚度均明显降低(均P<0.05);与20、30 mg/kg组比较,10 mg/kg组血清NE、MPO、IL-6、TNF-α含量、肺组织含水量、肺泡间隔厚度均明显降低(P<0.05).结论 西维来司钠能减轻大鼠烟雾吸入性肺损伤早期炎症反应及肺水肿,其中,10 mg/kg剂量处理效果优于其他剂量.%Objective To investigate the effects of sivelestat sodium on early inflammatory reaction in rats with smoke inhalation injury. Methods Forty SPF male SD rats were randomly divided into 5 groups:normal control group (A), injury group (B), smoke inhalation treated with 10 mg/kg sivelestat sodium group (C), smoke inhalation treated with 20 mg/kg sivelestat sodium group (D) and smoke inhalation treated with 30 mg/kg sivelestat sodium group (E), 8 rats for each group. After smoke inhalation injury model was established, the treatment groups were intraperitoneally injected sivelestat sodium 10 mg/kg, 20 mg/kg and 30 mg/kg separately. B group was treated with the same volume of physiological saline. After 24 hours,ELISA was used for detecting serum contents of neutrophil elastase (NE), myeloperoxidase (MPO), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in five groups. Meanwhile the water content of lung tissue was measured, and the pathological changes were observed by HE staining. The thickness of alveolar septum was measured and compared between groups. Results Compared with control group, the serum levels of NE, MPO, IL-6, TNF-α, water content of the lung tissue and thickness of alveolar septum were significantly higher in other four groups (P<0.05). Compared with injury group, the serum levels of NE, MPO, IL-6, TNF-α, water content of the lung tissue and thickness of alveolar septum were significantly lower in treatment groups (P<0.05). Compared with 20 mg/kg treatment group and 30 mg/kg treatment group, the serum levels of NE, MPO, IL-6, TNF-α, water content of the lung tissue and thickness of alveolar septum were significantly lower in 10 mg/kg treatment group (P<0.05). Conclusion The result shows that sivelestat sodium can reduce the early inflammatory reaction of rats with smoke inhalation injury and attenuates the lung edema. In this experiment, the treatment effect of 10 mg/kg sivelestat sodium is better than other treatment doses.