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山东大学学报(医学版) ›› 2011, Vol. 49 ›› Issue (5): 34-37.

• 论文 • 上一篇    下一篇

γ-氨基丁酸能系统对肺上皮细胞增殖的影响

徐静文1,刘勇2,张德普3,赵东波4,李景新3   

  1. 1.中山大学中山医学院, 广州 510080; 2.山东大学齐鲁儿童医院神经科, 济南 250022;
    3.山东大学医学院生理所, 济南 250012; 4.山东省肿瘤医院胸外科, 济南 250117
  • 收稿日期:2011-02-15 出版日期:2011-05-10 发布日期:2011-05-10
  • 通讯作者: 李景新(1971- ),男,硕士生导师,副教授,主要从事外周γ氨基丁酸能信号系统的病理生理研究。 E-mail:ljingxin@sdu.edu.cn
  • 作者简介:徐静文(1988- ),女,主要从事神经递质及其受体的研究
  • 基金资助:

    山东省优秀中青年科学家科研奖励基金(BS2010SW029)

Effect of the GABAergic system on lung epithelial cell proliferation 

XU Jing-wen1, LIU Yong2, ZHANG De-pu3, ZHAO Dong-bo4, LI Jing-xin3   

  1. 1. Zhongshan School of Medicine, Sun TatSen University, Guangzhou 510080, China;
    2. Department of Neurology, Qilu Children′s Hospital of Shandong University, Jinan 250022, China;
    3. Institute of Physiology, School of Medicine, Shandong University, Jinan 250012, China;
    4. Department of Thoracic Surgery, Shandong Tumor Hospital, Jinan 250117, China
  • Received:2011-02-15 Online:2011-05-10 Published:2011-05-10

摘要:

目的     研究γ-氨基丁酸(GABA ) 及其受体在肺上皮的表达及对肺上皮增殖的影响。方法     通过免疫组织化学染色及共聚焦显微镜检测肺组织及肺上皮细胞γ-氨基丁酸合成酶(GAD)及A型GABA受体(GABAA)的表达,用膜片钳方法研究GABA诱导的电流,用BrdU-ELISA和细胞计数法研究GABA对肺上皮细胞增殖的影响。结果     发现肺上皮细胞表达GAD及GABAA受体。通过膜片钳实验发现,在处于分裂期的上皮细胞,GABA诱导的电流明显增大。进一步通过细胞增殖实验发现,GABA通过GABAA受体发挥促增殖作用,且与细胞内钙增加有关。结论     在肺上皮细胞,GABA可作为一种旁分泌或自分泌因子通过细胞膜上的GABAA受体引起细胞膜去极化,从而使膜上电压依赖性钙通道开放,胞浆钙浓度升高,促进细胞增殖。为肺癌的预防及治疗提供新的理论基础,也可为肺组织损伤,特别是吸入性气体引起的肺上皮损伤的治疗提供新的手段。

关键词: γ-氨基丁酸;GABAA受体;肺上皮细胞;增殖

Abstract:

Objective    To explore the role of γ-amino-butyric acid (GABA) in lung epithelial cell proliferation. MethodsExpressions of GAD65/67 and GABAAR were identified by immunohistochemistry and confocal microscopy. The GABA-induced current was measured by whole cell patch clamp technique. The effect of GABA on cell proliferation was investigated by BrdU-ELISA and cell-counting assay. Results     GAD65/67 and GABAAR were localized in the airway epithelium and lung epithelial cell line A549 cells. In addition, the GABA-induced current was markedly increased in lung epithelial cells during mitosis. Further study showed that GABA induced lung epithelial cell proliferation in a GABAA receptor (GABAAR)- dependent manner. Voltage-dependent calcium channels were also involved in GABA-induced cell proliferation. Conclusion     The GABAergic signal system can regulate lung epithelial cell proliferation in an auto/paracrine manner, through GABAAR inducing cell membrane depolarization, opening voltage-dependent calcium channels and increasing cytoplasmic calcium. This finding may provide a new strategy for the treatment of lung cancer or lung epithelial injury.

Key words: γ-amino-butyric acid; GABAA receptor; Lung epithelial cells; Proliferation

中图分类号: 

  • R338.8
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