上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2018, Vol. 38 ›› Issue (4): 374-.doi: 10.3969/j.issn.1674-8115.2018.04.004

• 论著·基础研究 • 上一篇    下一篇

黄芪多糖APS- Ⅱ- 2对脂多糖所致绒毛膜羊膜炎诱发的肺泡化阻滞的改善作用

李文 1，谈珍 2，刘成博 1，王铮涛 3，张拥军 1   

  1. 1. 上海交通大学医学院附属新华医院新生儿科，上海200092；2. 上海交通大学医学院附属新华医院儿童血液/肿瘤科，上海200092；3. 上海中医药大学复方中药实验室，上海 201203
  • 出版日期:2018-04-28 发布日期:2018-05-03
  • 通讯作者: 张拥军，电子信箱：zhangyongjun@sjtu.edu.com。
  • 作者简介:李文（1991—），女，硕士生；电子信箱：liwen19910826@126.com。
  • 基金资助:
    国家自然科学基金（81671501）；上海市复方中药重点实验室开放课题基金（17DZ2273300）

Effect of APS-Ⅱ-2 on intra-amniotic lipopolysaccharide-induced alveolarization arrest in bronchopulmonary dysplasia model rats

LI Wen1, TAN Zhen2, LIU Cheng-bo1, WANG Zheng-tao3, ZHANG Yong-jun1   

  1. 1. Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; 2. Department of Paediatric Hematology/Oncology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; 3. Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Online:2018-04-28 Published:2018-05-03
  • Supported by:
    National Natural Science Foundation of China, 81671501;Opening Project of Shanghai Key Laboratory of Compound Chinese Medicines, 17DZ2273300

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摘要： 目的·探讨黄芪多糖APS-Ⅱ-2对脂多糖（lipopolysaccharide，LPS）所致绒毛膜羊膜炎诱发的肺泡化阻滞的改善作用及可能机制。方法·对孕16.5 d SD大鼠羊膜腔注射LPS，构建支气管肺发育不良模型。根据羊膜腔注入药物，将孕鼠随机分为对照组（Saline组）、LPS+Saline组、LPS+APS-Ⅱ-2组。LPS+APS-Ⅱ-2组新生鼠出生后第1～3日腹腔注射APS-Ⅱ-2溶液[50 mg/（kg·d）]；Saline组和LPS+Saline组腹腔注射等体积生理盐水。取第1、3日新生鼠肺组织，苏木精-伊红（H-E）染色观察病理改变。SD大鼠骨髓巨噬细胞培养，分为PBS组、LPS+PBS组、LPS+APS-Ⅱ-2组，利用全转录组测序技术（RNA-sequence）筛选APS-Ⅱ-2抑制炎症的可能靶点。结果· APS-Ⅱ-2可改善新生鼠肺组织病理状态，LPS+APS-Ⅱ-2组大鼠出生第1日肺泡数较LPS+Saline组增多（P0.033），第1、3日次级突起增多（P0.002，P0.026），第1、3日平均内衬间隔减小（P0.006，P0.004）。RNA-sequence结果显示APS-Ⅱ-2抑制一些炎症因子表达，如Toll样受体Tlr3、Tlr7、Tlr8；也促进一些有抗炎作用因子的表达，如花生四烯酸15-脂加氧酶Alox15和CD74。结论· APS-Ⅱ-2可通过调节炎症反应减轻LPS诱发的绒毛膜羊膜炎，进而改善支气管肺发育不良模型肺组织病理状态。

关键词: 支气管肺发育不良, 黄芪多糖, 绒毛膜羊膜炎, 炎症

Abstract:

Objective · To investigate the role of APS-Ⅱ-2 (a kind of plant-derived natural drug) on amelioration of chorioamnionitis-induced alveolarization arrest and the underlying mechanism. Methods · Bronchopulmonary dysplasia (BPD) model was constructedintra-amniotic injection of lipopolysaccharide(LPS) in SD rats (E16.5). The SD rats were randomly divided into control group (Saline group)、LPS model group (LPS+Saline group) and APS-Ⅱ-2administration group (LPS+APS-Ⅱ-2 group). Then neonatal rats in LPS+APS-Ⅱ-2 group were given an intraperitoneal injection with APS-Ⅱ-2 (50 mg/kg) for 3 consecutive days after birth, whereas rats in LPS+Saline group and Saline group were administrated with an equal amount of normal saline. To examine pathologic change of pulmonary in neonatal rats, hematoxylin-eosin (H-E) staining was performed at postnatal day1 and 3. Then bone marrow-derived macrophages (BMDMs) SD rats were detectedthe technology of RNA-sequence to research the immunomodulation of APS-Ⅱ-2.Results · APS-Ⅱ-2 administration group had drastically higher terminal air spaces (P0.033 at postnatal day1) and secondary septa counts at postnatalday1 and 3, respectively (P0.002, P0.026) than LPS-induced model group, while mean linear intercept was the opposite situation at postnatal day1and 3, respectively (P0.006, P0.004). The detection of RNA-sequence indicated that APS-Ⅱ-2 suppressed the of inflammatory cytokines such as Tlr3, Tlr7 and Tlr8 in BMDMs. Meanwhile, it also promoted some pleiotropic cytokines with anti-inflammatory effects such as Alox15 and Cd74. Conclusion · Administration of APS-Ⅱ-2 could improve the pathology of BPD, thereby supporting the ethno pharmacological uses of the plant. This effect may be directly causedmodulatory effects of APS-Ⅱ-2 on inflammation.

Key words: bronchopulmonary dysplasia, APS-Ⅱ-2, chorioamnionitis, inflammation

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