论著·基础研究

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
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  • 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
李文(1991—),女,硕士生;电子信箱:liwen19910826@126.com。

网络出版日期: 2018-05-03

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
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  • 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 published: 2018-05-03

Supported by

National Natural Science Foundation of China, 81671501;Opening Project of Shanghai Key Laboratory of Compound Chinese Medicines, 17DZ2273300

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。

本文引用格式

李文 1 , 谈珍 2 , 刘成博 1 , 王铮涛 3 , 张拥军 1 . 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[J]. 上海交通大学学报(医学版), 2018 , 38(4) : 374 . DOI: 10.3969/j.issn.1674-8115.2018.04.004

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.
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