γ-氨基丁酸能系统对肺上皮细胞增殖的影响

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

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．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． 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/Abstract

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

徐静文1，刘勇2，张德普3，赵东波4，李景新3 . γ-氨基丁酸能系统对肺上皮细胞增殖的影响[J]. 山东大学学报(医学版), 2011, 49(5): 34-37.

XU Jing-wen1， LIU Yong2, ZHANG De-pu3, ZHAO Dong-bo4, LI Jing-xin3. Effect of the GABAergic system on lung epithelial cell proliferation [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(5): 34-37.

参考文献

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed