柴油废气颗粒对大鼠气道反应性及肺部病理改变影响

Effects of diesel exhaust particles on airway hyperresponsiveness and changes of the lung pathology in rats

目的探讨空气污染物中柴油废气颗粒(DEP)的吸入对哮喘模型大鼠的气道反应性和肺部病理改变的影响。方法选择Wistar大鼠60只随机分为A组为正常对照组;B组为哮喘模型组,利用卵清白蛋白(OVA)制备哮喘模型;C、D、E、F组于第1天开始用OVA攻击(方法与B组相同),之后再给予吸入DEP各1、2、3、4周。每只大鼠均于最后一次雾化结束后次日处死,并测定每只大鼠气道阻力(RL)30min的变化,观察支气管肺泡灌洗液(BALF)中炎症细胞的百分比和肺组织病理形态学改变,采用酶联免疫吸附试验法测定血清中总IgE的浓度变化。结果抗原激发后B组RL比A组增高,E、F组的RL比B组明显增高,之间比较差异有统计学意义(F=156.186,P<0.01),RL的增高与DEP吸入时间呈显著正相关(r=0.948,P<0.01);血清中总IgE的浓度在B组较A组明显增加,之间比较差异有统计学意义(F=2.490,P<0.01);C、D、E、F组BALF中嗜酸性粒细胞占细胞总数的百分比(EOS%)逐渐增高,与B组比较差异有统计学意义(F=23.240,P<0.01),实验组BALF中中性粒细胞的浸润逐渐增多,E、F组BALF中的中性粒细胞数占细胞总数的百分比较B组明显增高,与之比较差异有统计学意义(F=36.329,P<0.01);肺组织病理切片中可以看到A组上皮细胞完整,气道周围未见炎症细胞的浸润,以纤毛柱状上皮细胞为主,仅有少量的杯状细胞,基底膜未见纤维化,实验组随着DEP的1、2、3、4周的吸入,逐渐出现上皮细胞的减少、中断、脱落,杯状细胞大量增生,气道周围的炎症细胞的浸润及基底膜的纤维化等改变。结论柴油DEP的吸入可加重哮喘大鼠的气道高反应性和肺部的炎症反应。

Objective To investigate the effects of diesel exhaust particles （DEP） in air pollutants on airway hyperresponsiveness and changes of lung pathology in the asthma model rats. Methods Wistar rats were randomly divided into 6 groups, with 10 rats in each group. Group A was the control group; Group B was the animal model group which was OVA-sensitized-challenged. Group C, D, E, F were sensitized to ovalbumin （OVA）, inhaled DEP for 1,2,3,4 weeks and challenged with 3 % OVA. 30 min RL of each rat was evaluated, and the number of eosinophils cells in brouchialveolar lavage fluid （BALF） and the pathological changes of lung tissue were observed. Results The airway hyperresponsiveness of group B increased significantly compared with that of group A, while hyperresponsiveness in Group B was significantly different from that in group E and F （ F = 156. 186, P 〈 0. 01 ）. The higher RL was positively related to the time of DEP exposure （ r = 0. 948, P 〈 0. 01 ） ; The concentration of IgE was significantly different between group A and B （ F = 2. 490, P 〈 0. 01 ）. Eosinophils count of BALF in group B was significantly more than that of the control group （ F =23.240 ,P 〈0. 01 ）. Neutrophlis of major inflammatory cells were infiltrated one week after DEP inhalation. Neutrophlis counts in group B were significantly different from that in group E and F （ F = 36. 329, P 〈 0. 01 ） ; the pathological changes of lung showed epithelial shedding, infiltration of inflammatory cells in peribronchial and fibrosis on the basement membrane. Conclusion The exposure of DEP might exacerbate airway hyperresponsiveness and elicited pathological changes in lung tissue of asthma model rats.