细颗粒物PM2．5对支气管哮喘小鼠气道炎症影响研究

Effect of PM2.5 on airway inflammation in asthmatic mice

目的探讨细颗粒物PM2.5对支气管哮喘（简称哮喘）小鼠气道炎症的影响，明确其是否可引起重症哮喘气道改变。方法①无特殊病原体（SPF）级Balb／c小鼠随机数字分为正常对照组（NC组）、哮喘组（AC组）、哮喘＋低剂量PM2.5组（AP—L）、哮喘＋高剂量PM2.5组（AP—H）。②卵蛋白（OVA）致敏、气道激发。AP两组雾化前30min，气管滴注不同浓度PM2.5混悬液100μl。③末次激发24h后，小鼠行肺功能检测，评价气道阻力；支气管肺泡灌洗液（BALF）离心沉渣，行炎症细胞计数；酶联免疫吸附试验法检测小鼠血清、BALF中IL-17的水平；小鼠肺组织行HE染色观察气道炎症情况。结果①成功建立OVA诱导哮喘急性小鼠模型；②4组小鼠基础Re相似，不同剂量Ach激发中，AC与AP两组的平均Re值明显高于NC组，AP两组平均Re值较AC组明显升高，并且AP两组间存在剂量依赖性（P〈0．05）。AC、AP两组细胞总数、中性粒细胞均较NC明显升高，AP两组较AC组明显升高，AP两组之间存在剂量依赖性（P〈0．05）。AC、AP两组血清、BALF中IL-17较NC组明显升高，AP两组较AC组明显升高，AP两组存在剂量依赖性（P〈0．05）。HE染色显示，NC组肺组织基本正常，AP—H炎症浸润最为明显，AC、AP—L组气道壁管腔增厚程度较AP—H组减轻，管壁周围炎性细胞浸润以淋巴细胞和嗜酸粒细胞为主。结论大剂量细颗粒物PM2.5暴露可加重哮喘小鼠气道炎症和气道高反应性，使气道发生重症哮喘的病理改变。

Objective To evaluate the effect of PM2.5 on airway inflammation in asthmatic mice,to verify the severe asthma airway inflammation induced by PM2.5. Methods （1） BALB/c mice were randomly divided into four groups： the control group （NC group）, the asthma group （AC group）, the asthma＋low dose PM25 group （AP L group）, the asthma＋high PM2.5 group （AP-H group）. （2）Mice in the last three groups were sensitized and challenged by OVA. Mice in the two PM2.5 group were given 100 μl PM2.5 suspension. （3）Airway responsiveness to acetylcholine chloride （Ach） was measured in mice 24 h after the last challenge. Bronchoalveolar lavage fluid （BALF） was centrifuged and total cell and neutrophil cell were counted, enzyme linked immunosorbent assay were used to determine IL 17 levels in BALF and serum. The airway inflammatory infiltration was detected by haematoxylin and eosin （HE） staining. Results （1）An OVA-induced mouse models with acute asthma were successfully established. （2） No significant difference was found in baseline airway resistance among the four groups. At dose of Ach from 10 to 270 μg· kg^-1 the airway resistance in the AC, AP two groups was obvious increased compared with the NC group, the AP two groups had significant greater airway resistant than AC group in a dose- dependent manner （ P 〈 0.05）. Very few inflammatory cells were detected in NC mice, a significant increase in total and neutrophil cell number was exhibited in AC and AP animals, the AP two groups had greater increase compared with AC group in a dose-dependent manner （ P〈0.05）. Levels of IL-17 in BALF and serum were significantly increased in AC and AP groups than NC group, the AP two groups had greater increase compared with AC group in a dose-dependent manner （ P 〈0.05）. In the following hematoxylin and eosin, the structure of lung tissue in NC group is normal, the inflammation of air flue in AP-H group is obvious, while airway inflammation in AC and AP-L group attenuated. Conclusions Magnetic exposure to PMza may aggravate the airway inflammation and airway hyperresponsiveness in asthmatic mice and form severe asthma.