| 摘要: |
| 目的 研究氟比洛芬酯(flurbiprofen axetil, FA)对脂多糖(lipopolysaccharides,LPS)吸入性肺损伤的预防作用,为临床吸入性肺损伤的治疗提供理论依据。 方法 96只成年雄性Sprague-Dawley大鼠随机分为4组: 生理盐水阴性对照组(NS组)、模型组(LPS组)、脂肪乳剂预处理对照组(Lip+LPS组)和FA预处理组(FA+LPS组),每组24只。NS组大鼠气管内滴注 1 mL/kg 生理盐水,其余3组大鼠气管内滴注LPS 1 mL/kg制模。Lip+LPS组和FA+LPS组大鼠分别在制模前1 h经尾静脉注射20%脂肪乳剂1 mL/kg和10 mg/mL的FA注射液1 mL/kg。以气管内注药后第1、6、12、24小时为观察终结时间点,分别测定各组大鼠的动脉血气、肺组织湿/干质量(W/D)比,观察肺组织病理改变,检测肺组织中过氧化物酶增殖体激活受体α(peroxisome proliferators activated receptor-α, PPAR-α)和过氧化物酶增殖体激活受体γ(PPAR-γ)表达的变化及血清中肿瘤坏死因子α(tumor necrosis factor α, TNF-α)浓度。 结果 LPS组和Lip+LPS组大鼠出现了明显的肺组织结构毁损和炎性反应,PPAR-α、PPAR-γ的mRNA表达较NS组降低(P< 0.05),TNF-α浓度较NS上升(P<0.05);FA+LPS 组较LPS组和Lip+LPS组肺组织病理改变有所减轻,在致炎后6、12和24 h时动脉血氧分压(PaO2)上升、肺组织病理半定量评分下降(P< 0.05),而大鼠肺组织中PPAR-α与PPAR-γ mRNA表达量在各时间点则有不同程度的升高,致炎 6 h 后升高(P< 0.05),TNF-α浓度在时间点则有不同浓度的降低,致炎1 h后降低(P<0.05)。 结论 FA预处理对LPS吸入性肺损伤大鼠具有一定的抗炎和肺保护作用,其机制与FA预处理能上调肺组织内PPAR-α、PPAR-γ的mRNA表达,以及下调血清中TNF-α的表达有关。 |
| 关键词: 氟比洛芬 吸入性肺损伤 PPARα PPARγ 肿瘤坏死因子α NF-κB |
| DOI：10.3724/SP.J.1008.2015.1180 |
| 投稿时间：2015-03-22修订日期：2015-07-15 |
| 基金项目: |
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| Flurbiprofen axetil preconditioning allivates inhalation lung injury in rats |
| YAN Wei-min1,JIANG Hong2,CHEN Wan-tao3* |
(1. Department of Anesthesiology, Shanghai International Medical Center, Shanghai 201318, China;
2. Department of Anesthesiology, Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China;
3. Department of Oral and Maxillofacial Surgery, Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
*Corresponding author.) |
| Abstract: |
| Objective To investigate the protective effects of flurbiprofen axetil(FA) on inhalation lung injury induced by lipopolysaccharides(LPS)inhalation in rats, so as to provide evidence for applying FA in treating inhalation lung injury in clinic. Methods A total of 96 adult male Sprague-Dawley rats were evenly randomized into four groups(n=24): saline negative control group(NS group), model group(LPS group), lipid emulsion preconditioning control group(Lip+LPS group), and FA preconditioning group(FA+LPS group). The model of inhalation lung injury was established with endotracheal instillation of LPS(1 mL/kg)in all experimental groups. NS group was identical to the other three groups except that saline(1 mL/kg)was administered instead of LPS. Lipid emulsion(20%,1 mL/kg)or FA injection(1 mL/kg,10 mg/mL)was intravenously injected via vena caudalis 1 hour before LPS in Lip+LPS and FA+LPS groups, respectively. Rats were sacrificed at 1 h, 6 h, 12 h and 24 h after LPS injection and assigned to 1 h, 6 h, 12 h and 24 h subgroups(n＝6). The arterial blood gas was analyzed and the lungs were removed for determination of the wet/dry mass(W/D)ratio and evaluation of histological injury in all groups. Real-time PCR was used to detect the mRNA levels of PPAR-α and PPAR-γ in rats lung homogenates. The concentration of tumor necrosis factor-alpha(TNF-α)in rat serum was determined by ELISA. Results The rats in LPS and Lip+LPS groups showed damaged structure of lung tissue and inflammation. The mRNA levels of PPAR-α and PPAR-γ in the lung tissues of LPS group were significantly lower than those of NS group(P< 0.05). The serum concentration of TNF-α of LPS group was significantly higher than that of NS group (P<0.05). The pulmonary lesions in FA+LPS group were ameliorated compared with those in LPS and Lip+LPS groups. Pressure of oxygen in arterial blood(PaO2)was signficantly higher and semi-quantitative pathological score of lung was signficanlty lower in FA+LPS group than those in LPS and Lip+LPS group at 6 h, 12 h and 24 h after injection(P< 0.05). The mRNA levels of PPAR-α and PPAR-γ in rat lung tissues of FA+LPS group were signficanlty higher than those of LPS and Lip+LPS groups at all times, especially, at 6 h after the intravenous injection of LPS(P< 0.05). The serum concentration of TNF-α of FA+LPS group was significantly lower than that of LPS and Lip+LPS groups at all times, expecially, at 1 h after the intravenous injection of LPS (P<0.05). Conclusion FA preconditioning can alleviate the inflammation and protect inhalation injury to lung tissues induced by LPS in rats, which may involve the up-regulation of PPAR-α and PPAR-γ mRNA levels in rat lung tissues and the down-regulation of serum TNF-α. |
| Key words: flurbiprofen inhalation lung injury PPARα PPARγ tumor necrosis factor-α NF-κB |
