张晓雅+冯淬灵+孟玉凤+杜建超+岑锦裳+魏永杰

摘要：目的 觀察PM2.5致辅助性T细胞17（TH17）与调节性T细胞（Treg）失衡诱发的大鼠肺损伤及不同中药治法的干预作用。方法 将SPF级雄性Wistar大鼠随机分为正常组、模型组、中药1组和中药2组。采用气道滴注方法建立PM2.5致肺损伤模型，模型组和正常组予生理盐水灌胃，中药1组和及中药2组分别予玉屏风散及过敏煎合止嗽散灌胃。ELISA检测各组肺泡灌洗液（BALF）及血清白细胞介素（IL）-17、IL-10、IL-8、中性粒细胞弹性蛋白酶（NE）、黏蛋白（MUC）5AC含量；免疫组化检测肺组织Foxp3、IL-17的表达。结果 与正常组比较，模型组血清和BALF IL-8、IL-17、NE、MUCAC含量显著升高，IL-10含量明显降低（P<0.05，P<0.01），肺组织IL-17蛋白表达明显增加、Foxp3蛋白表达明显降低（P<0.01）；与模型组比较，中药1组及中药2组血清和BALF IL-8、IL-17、NE含量明显降低，BALF IL-10明显升高，中药2组血清IL-10明显升高（P<0.05），肺组织IL-17蛋白表达明显降低、Foxp3蛋白表达明显增加（P<0.01），病理学变化明显改善。结论 PM2.5可通过引起Th17/Treg失衡诱发肺损伤，玉屏风散及过敏煎合止嗽散均可明显改善PM2.5致大鼠肺组织病理损害，并可改善PM2.5导致的TH17/Treg失衡。

关键词：玉屏风散；过敏煎合止嗽散；PM2.5；肺损伤；辅助性T细胞17；调节性T细胞；大鼠

DOI：10.3969/j.issn.1005-5304.2017.04.012

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2017）04-0045-05

Effects of Yupingfeng Powder and Guomin Decoction Combined with Zhisou Powder on Lung Injury Rats Caused by Imbalance of Th17/Treg Induced by PM2.5 ZHANG Xiao-ya1，2， FENG Cui-ling3， MENG Yu-feng1， DU Jian-chao1， CEN Jin-shang4， WEI Yong-jie5 （1. Dongzhimen Hospital Attached to Beijing University of Chinese Medicine， Beijing 100700， China； 2. Cangzhou Central Hospital， Cangzhou 061014， China； 3. Peoples Hospital of Peking University， Beijing 100044， China； 4. Sinopharm Group Guangdong Medi-World Pharmaceutical Co， Guangzhou 528303， China； 5. State Key Laboratory of Environmental Criteria and Risk Assessment， Chinese Research Academy of Environmental Sciences， Beijing 100012， China）

Abstract： Objective To observe the lung injury of rats caused by PM2.5 induced imbalance of TH17/Treg immune system and the intervention effect of two different TCM treatments. Methods Wistar male rats were randomly divided into normal group， model group， TCM-treated group1 and TCM-treated group 2. PM2.5-induced lung injury model was established by airway instillation. Model group was given normal saline for gavage. TCM- treated group 1 and 2 were given Yupingfeng Powder and Guomin Decoction combined with Zhisou Powder for gavage. The pathological changes of bronchial and lung tissues， the contents of IL-8， IL-10， IL-17， NE， and MUC5AC in serum and BALF were compared， and the expressions of Foxp3 and IL-17 in lung tissue of each group were analyzed. Results Compared with normal group， the contents of IL-8， IL-17， NE and MUC5AC in serum and BALF of model group increased significantly， while IL-10 decreased significantly （P<0.05， P<0.01）； the expression of IL-17 increased significantly and the expression of Foxp3 decreased significantly in lung tissue （P<0.01）. Compared with model group， the contents of IL-8， IL-17， and NE decreased in TCM-treated group 1 and 2， while the content of BALF IL-10 increased significantly （P<0.05）. The content of IL-10 in serum increased significantly in TCM-treated group 2 （P<0.05）； the protein expression of IL-17 of lung issue decreased significantly， and the protein expression of Foxp3 increased significantly （P<0.01）. The pathological changes were improved significantly. Conclusion PM2.5 can induce lung injury caused by the imbalance of TH17/Treg. Both two treatments can significantly improve the lung injury induced by PM2.5 and the imbalance of TH17/Tregs immune system.endprint

Key words： Yupingfeng Powder； Guomin Decoction combined with Zhisou Powder； PM2.5； lung injury； TH17； Treg； rats

近年来，空气污染加重，雾霾频现。细颗粒物（paticulate matter，PM）是雾霾的主要成分。PM2.5有粒径小、面积大、活性强，易附带有毒、有害物质，且在大气中的停留时间长、输送距离远等特点。PM2.5的这些特性决定其表面可以吸附更多有害物质，并且可以自如避开呼吸系统的天然屏障如鼻毛、支气管纤毛等而进入细小支气管及肺组织内，对人体造成更大的损伤。本研究运用过敏煎合止嗽散及玉屏风散干预PM2.5致大鼠肺损伤模型。前者可祛风固卫、宣肺止咳，后者偏于益气固表、防邪外侵。初步探讨2种不同治法的干预作用及机制。

1 实验材料

1.1 动物

清洁级雄性Wistar大鼠24只，鼠龄6～8周，体质量（200±20）g，北京维通利华实验动物技术有限公司，合格证号11400700124029。饲养于20～25 ℃、12 h光照清洁的动物房，自由饮水，进食标准饲料。……