吡非尼酮对舰船烟雾所致吸入性肺损伤大鼠的防护作用

Preventive effect of pirfenidone against inhalation lung injury caused by ship smoke in rats

目的探讨吡非尼酮(PFD)对舰船烟雾所致吸入性肺损伤大鼠的防护作用。方法将健康成年雄性Wistar大鼠放入自制发烟装置,吸入舰船烟雾15 min建立吸入性肺损伤大鼠模型。吸入烟雾前30 min,正常对照组大鼠和烟雾吸入损伤组分别ip含5%二甲亚砜的生理盐水2 mL,PFD组ip PFD300 mg·kg^(-1)(溶于5%二甲亚砜的生理盐水)2 mL。分别于12,24和48 h每组各取6只大鼠,腹主动脉取血,检测动脉血气。双抗体夹心法检测白细胞介素6(IL-6)、IL-17和肿瘤坏死因子α(TNF-α)水平;取右肺前叶,计算肺含水率;留取右肺中叶,检测肺组织中丙二醛(MDA)含量;取右肺下叶经4%甲醛固定后做病理切片,苏木精-伊红染色,光镜观察。结果与正常对照组比,舰船烟雾吸入损伤暴露后12,24和48 h,烟雾吸入损伤组各时相点O_2分压(paO_2)降低,CO_2分压(paCO_2)升高(P<0.05),肺含水率水平升高(P<0.05),血清中IL-6,IL-17和TNF-α水平升高(P<0.05),肺组织匀浆中MDA含量增加(P<0.05)。与烟雾吸入损伤组相比,PFD组大鼠动脉血中paO_2水平升高,paCO_2及肺含水率降低(P<0.05),大鼠血清中IL-6,IL-17和TNF-α水平降低,组织中MDA含量降低(P<0.05)。病理观察可见,PFD组较舰船烟雾吸入损伤组肺组织水肿减轻,肺泡腔渗出及炎症细胞浸润减少。结论 PFD可通过抑制IL-6等相关炎症因子的释放减轻舰船烟雾致大鼠吸入性肺损伤。

OBJECTIVE To investigate the protective effect of pirfenidone（PFD） against inhalation lung injury induced by ship smoke in rats.METHODS Fifty-four healthy adult male Wistar rats were divided into three groups by random digital table：normal control group,smoke inhalation injury group and PFD 300 mg·kg^-1 treatment group.Each group had three phase points of 12,24 and 48 h,with 6 rats at each time phase point.A rat model was established by inhalation lung injury with a selfmade smoke device.The normal control group and smoke inhalation injury group were ip given saline 2 mL containing 5% of dimethyl sulfoxide,while PFD group ip PFD 300 mg·kg^-1（dissolved in 5% dimethyl sulfoxide saline） 2 mL.After 30 min,blood from the abdominal aorta.In normal control group,rats were placed in a normal air environment,while the smoke inhalation injury group and PFD group were exposed to a ship smoke environment for 15 min.Blood samples were collected from the abdominal aorta at different time phase points,and blood gas contents of interleukin-6（IL-6）,IL-17 and tumor necrosis factor-α（TNF-α） were detected.The water content of lung tissue and the content of malondialdehyde（MDA） in lung tissue were tested.The lower lobe of the right lung was fixed by 4% formaldehyde solution for pathological hematoxylin eosin staining.RESULTS Compared with the normal control group,after exposure to smoke for 12,24,and 48 h,the level of partial pressure of oxggen（paO2） in smoke inhalation injury group was decreased,arterial blood carbon dioxide partial pressure（paCO2） increased（P〈0.05）,the percentage of water in lung tissue was increased（P〈0.05）,the contents of IL-6,IL-17 and TNF-α was increased（P〈0.05）,and the contents of MDA in lung tissue homogenate were increased（P〈0.05）.Compared with the smoke inhalation injury group,the level of paO2 in PFD group was increased（P〈0.05）,paCO2 and the water content of lung tissue decreased（P〈0.05）,the contents of IL-6,IL-17,TNF-α decreased（P〈0.05）,so did the content of MDA in lung tissue.Pathological observation showed that lung tissue edema,alveolar exudation and inflammatory cell infiltration decreased in PFD group compared with smoke inhalation injury group.CONCLUSION PFD has a protective effect against lung tissue injury in ship smoke inhalation rats.It is possible to inhibit the generation and release of some inflammatory mediators,thus alleviating the lung injury induced by ship smoke inhalation in rats.