可吸入颗粒物2.5对大鼠肺纤维化的影响及糖皮质激素的干预作用

摘要

目的:观察大鼠气道内滴入PM2.5引起急性肺损伤的同时,是否导致肺纤维化以及糖皮质激素对PM2.5所致肺损伤和肺纤维化是否具有干预作用.方法:将150只大鼠,随机分为对照组、PM2.5染毒组(实验组)、糖皮质激素干预组(干预组).实验组:大鼠经气管内滴入PM2.5(60mg/kg)染毒,每周2次,连续4周.干预组:大鼠染毒的同时,给予地塞米松(5mg· kg-1·d-1)腹腔注射,每日1次.对照组:0.9％氯化钠液替代PM2.5悬液.于第5天和28天分二批处死大鼠并留取标本.分别测定大鼠BALF及血清中IL-6、TNF-α、TP、PINP、PⅢNP的浓度;大鼠左肺组织行HE染色和Masson染色,观察肺组织的炎症程度和胶原纤维分布;大鼠右肺组织测定羟脯氨酸含量,左肺测定湿/干重比.结果:染毒后第5天,实验组与干预组大鼠血清与BALF中IL-6、TNF-α、PINP、PⅢNP浓度均较对照组有明显升高(P＜0.05);与实验组大鼠相比,干预组大鼠血清与BALF中IL-6与TNF-α浓度有明显降低(P＜0.05),PINP与PⅢNP水平无明显差异;三组大鼠右肺组织HYP含量无明显差异.染毒后第28天,血清与BALF中IL-6、TNF-α、PINP、PⅢNP浓度,实验组大鼠较干预组和对照组均有明显升高(P＜0.05);干预组大鼠肺组织HYP含量及湿/干重比较实验组明显降低,但均较对照组明显升高(P＜0.05).结论:PM2.5可导致大鼠急性肺损伤和肺纤维化,而地塞米松干预后能改善和抑制肺部炎症改变和纤维化形成.%Objective:To observe the effect of PM2.5 on acute lung injury and concomitant pulmonary fibrosis and to assess the intervention of glucocorticoid in healthy rats.Methods:150 healthy rats were instilled into trachea with three different solutions twice per week for four weeks:experimental group with PM2.5 60mg/ kg;intervene group with PM2.5 and hexadecadrol 5mg/kg/d per day;control group with saline.All rats were killed 5 days and 28 days separately and specimens were taken for the following tests.BALF and serum were left for measurement of IL-6、TNF-α、TP、PINP and PⅢNP concentration,left lung tissue were left for HE and Masson dyeing to observe the degree of inflammatory cell infiltration and collagenous fiber distribution,right lung tissue were left for measurement of hydroxyproline concentration.Results:5 days after PM2.5 trachea instilled,compared with the control group,the concentration of BALF and serum IL-6、TNF-α、PINP and PⅢ NP in the experimental and the intervene group were obviously higher(P ＜ 0.05);compared with the experimental group,the concentration of IL-6 and TNF-α were obviously lower (P ＜ 0.05) in the intervene group;the hydroxyproline concentration of the three subgroups were on the same level and without obviously difference.28 days after PM2.5 instilled,the concentration of IL-6、TNF-α 、PINP and PⅢNP in BALF and serum were tested higher in the experimental group than the control group and the intervene group(P ＜ 0.05);the hydroxyproline concentration and the wet/dry ratio of the intervene group was obviously lower than the experimental group,while all were much higher than the control group (P ＜ 0.05).Conclusion:PM2.5 inhalation can result in the acute lung injury and pulmonary fibrosis in healthy rats,which can be improved and inhibited by the intervention of glucocorricoid.