上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 专题报道（新生儿基础与临床研究） •    下一篇

茶碱通过炎性调节改善羊膜腔注射LPS诱发的新生鼠肺泡化阻滞

何 华1，陈 菲1，李慧萍2，倪文思1，李健辉1，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.复旦大学附属儿科医院， 上海 201102
  • 出版日期:2013-07-28 发布日期:2013-08-22
  • 通讯作者: 张拥军, 电子信箱: shanghaiyjzhang@yahoo.com.cn。
  • 作者简介:何 华（1986—）， 女， 硕士生; 电子信箱: lotus19861123@sina.com。
  • 基金资助:

    国家自然科学基金(81270729)；上海市科委自然基金 (11ZR1423800)

Theophylline improves intra-amniotic LPS-induced alveolar arrest through inflammatory regulation in neonatal rats

HE Hua1, CHEN Fei1, LI Hui-ping2, NI Wen-si1, LI Jian-hui1, ZHANG Yong-jun1   

  1. 1.Department of Neonatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine， Shanghai 200092, China; 2.Children's Hospital, Fudan University, Shanghai 201102, China
  • Online:2013-07-28 Published:2013-08-22
  • Supported by:

    National Natural Science Foundation of China, 81270729; Shanghai Science and Technology Committee Foundation, 11ZR1423800

PDF (PC)

1239

摘要：

目的 探讨茶碱对宫内绒毛膜羊膜炎诱发肺泡化阻滞病理改变的改善作用及可能机制。方法 SD孕鼠（孕16.5 d）经羊膜腔注射脂多糖（LPS）诱发宫内绒毛膜羊膜炎，另取对照SD孕鼠（孕16.5 d）经羊膜腔注射等量生理盐水。注射LPS的孕鼠所产新生鼠随机分为LPS+theo组和LPS+saline组，其中LPS+theo组于颈部皮下注射茶碱（1次/d）至第7天，LPS+saline组于颈部皮下注射等量生理盐水（1次/d）至第7天。对照孕鼠所产新生鼠的处理同LPS+saline组（对照组）。分组干预后第7天，取各组新生鼠肺组织，制作苏木精-伊红(HE)染色切片和细胞因子抗体芯片，观察肺组织病理学改变，检测炎症性细胞因子的表达情况。结果 组织病理学检查发现，与对照组比较，LPS+saline组肺泡计数和次级突起计数明显减少（P<0.05），LPS+theo组肺泡计数和次级突起计数显著多于LPS+saline组（P<0.05）；抗体芯片检测结果显示，LPS+ saline组新生鼠肺组织中炎症因子γ干扰素、白介素α、白介素6和CXCR4的表达均较对照组明显上调；与LPS+ saline组比较，LPS+theo组中炎症因子肿瘤坏死因子α、巨噬细胞炎症蛋白1α和巨噬细胞炎症蛋白2的表达明显下调（分别下调37.4、12.5、8.6倍），而抗炎症因子TGF-β1、TGF-β2和TGF-β3的表达明显上调（分别上调2.4、56.9、17.8倍）。结论 茶碱能抑制炎症因子表达，上调抗炎症因子的表达，通过调节促炎与抗炎机制的平衡，减轻肺泡化阻滞的病理变化，提示茶碱对宫内绒毛膜羊膜炎诱发的支气管肺发育不良的病理过程具有改善作用。

关键词: 支气管肺发育不良, 茶碱, 绒毛膜羊膜炎, 炎症

Abstract:

Objective To investigate the role of theophylline on amelioration of chorioamnionitis-induced alveolar arrest, and explore the potential mechanism. Methods Chorioamnionitis was induced by intra-amniotic injection of lipopolysaccharides (LPS) in SD rats (E16.5), and the same amount of normal saline was intra-amniotically injected in control SD pregnant mice (E16.5). Pups of same litter with intra-amniotic injection of LPS were randomly divided into LPS+theo group and LPS+saline group. In LPS+theo group, pups were injected subcutaneously in the neck with theophylline once a day until the seventh day, and the same amount of normal saline instead in LPS+saline group. Pups with intra-amniotic injection of normal saline obtained identical postnatal treatment as LPS+saline group, which was defined as control group. Seven days after treatment, the lungs of neonatal rats were harvested, sections with HE staining and cytokine antibody arrays were prepared, the pathological changes of lung tissues were observed, and the expression of inflammatory cytokines was determined. Results Histopathological examination revealed that the alveolar counts and secondary septa counts in LPS+saline group were significantly smaller than those in control group (P<0.05), and the alveolar counts and secondary septa counts in LPS +theo group were significantly larger than those in LPS+saline group (P<0.05). The detection of antibody arrays indicated that the expression of inflammatory cytokines such as interferon γ (IFN-γ), interleukin (IL)-α, IL-6 and chemokine receptor type 4 (CXCR4) in lung tissues of neonatal rats in LPS+saline group was higher than that in control group, the expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), macrophage inflammatory protein (MIP)-1α and MIP-2 in LPS+theo group was significantly lower than that in LPS+saline group (decreased by 37.4 times, 12.5 times and 8.6 times respectively), and the expression of anti-inflammatory cytokines such as transforming growth factor (TGF)-β1, TGF-β2 and TGF-β3 in LPS+theo group was significantly higher than that in LPS+saline group (increased by 2.4 times, 56.9 times and 17.8 times respectively). Conclusion Theophylline can inhibit the expression of pro-inflammatory cytokines, increase the expression of anti-inflammatory cytokines, and relieve alveolar arrest through regulating the balance between pro- and anti-inflammatory cytokines. Theophylline may play a role in the amelioration of chorioamnionitis-induced bronchopulmonary dysplasia.

Key words: bronchopulmonary dysplasia, theophylline, chorioamnionitis, inflammation