The central glial cell line-derived neurotrophic factor (GDNF) regulates pulmonary function in asthmatic rats.

The central glial cell line-derived neurotrophic factor (GDNF) regulates pulmonary function in asthmatic rats.
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中央胶质细胞源性神经营养因子(GDNF)调节哮喘大鼠的肺功能

DOI:
10.21037/atm-22-6338
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发表时间:
2023-01-31
影响因子:
--
通讯作者:
Chen, Zhe
Chen, Zhe
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Xiaoyan;Wang, Yuehan;Chen, Xuelian;Li, Tinglei;Zhang, Shu;Dong, Rong;Chen, Zhe

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背景哮喘是一种常见的气道慢性炎症性疾病,其发病机制尚未完全阐明。本研究旨在探讨胶质细胞源性神经营养因子(GDNF)在哮喘发作中的作用。方法建立哮喘大鼠模型。采用免疫组化法(IHC)观察GDNF在气道和脑组织中的表达,酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液(BALF)中GDNF的浓度。侧脑室注射GDNF及其抗体后,记录哮喘大鼠肺功能,检测支气管肺泡灌洗液(BALF)中γ干扰素(IFN-γ)和白细胞介素4(IL-4)的含量。结果GDNF在哮喘大鼠肺组织中的表达明显增加。在中枢神经系统(CNS),GDNF阳性免疫反应物质观察到在多个脑区,包括内侧杏仁核(MeA),室旁核(PVN),皮质,孤束核(NTS)。侧脑室注射GDNF后,哮喘大鼠的哮喘症状和气道炎症明显加重,侧脑室注射GDNF抗体可改善哮喘症状和气道炎症。结论GDNF在哮喘大鼠肺和脑组织中表达增加。哮喘发作时,大鼠脑内GDNF表达增加,哮喘症状明显加重。
Background Asthma is a common chronic inflammatory disease of the airway, but the mechanism is still not fully understood. This study aimed to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on asthma attacks. Methods An asthmatic rat model was established. GDNF expression in the airway and brain was observed by immunohistochemistry (IHC), and the concentration of GDNF in bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay (ELISA). After injection of GDNF and its antibody into the lateral ventricle of asthmatic rats, the pulmonary function was recorded, and the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in BALF were tested. Results GDNF expressions were increased significantly in the lung tissues of asthmatic rats. In the central nervous system (CNS), GDNF-positive immunoreactive substances were observed in multiple brain regions, including the medial amygdala (MeA), paraventricular nucleus (PVN), cortex, and nucleus of solitary tract (NTS). After injection of GDNF into the lateral ventricles of asthmatic rats, the symptoms of asthma and airway inflammation were significantly aggravated, which could be improved by injection of GDNF antibody into the lateral ventricles. Conclusions GDNF expression is increased in the lung and brain in asthmatic rats. During an asthma attack, the increased GDNF expressions in the rat brain remarkably aggravate the asthmatic symptoms.
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