TRPC1对慢性阻塞性肺疾病慢性气道炎症的影响

目的探讨瞬时感受器电位通道C1(TRPC1)在慢性阻塞性肺疾病(慢阻肺)患者支气管黏膜上皮的表达水平及其与慢性气道炎症之间的关系。方法选取因不明原因肺部结节行纤维支气管镜检查的78例患者,依据慢性阻塞性肺疾病诊治指南分为慢阻肺组(46例)及对照组(32例),其中慢阻肺组再随机分为两个亚组:每日3次规律使用吸入型激素(ICS)布地奈德(ICS组,23例)及安慰剂(非ICS组,23例)治疗。所有受检查者均行支气管肺泡灌洗及支气管镜下刷检。Western Blot及qRT-PCR法检测刷检支气管上皮细胞内TRPC1表达水平,支气管肺泡灌洗液(BALF)行细胞学分类计数。酶联免疫吸附法检测BALF上清液中炎症介质白细胞介素13(IL-13)、成纤维生长因子2(FGF-2)表达水平。结果慢阻肺组支气管上皮细胞内的TRPC1 mRNA、蛋白表达水平明显高于对照组(P<0.05);ICS组的TRPC1表达水平低于非ICS组(P<0.05)。与对照组相比,慢阻肺组BALF中的中性粒细胞、巨噬细胞、淋巴细胞计数及IL-13、FGF-2水平均明显升高(P<0.05)。而ICS组BALF中的中性粒细胞、巨噬细胞、嗜酸性粒细胞、淋巴细胞计数及IL-13、FGF-2表达水平则低于非ICS组(P<0.05)。相关性分析结果显示,TRPC1 mRNA和蛋白表达水平与肺功能第一秒用力呼吸容积(FEV 1)占预计值百分比(FEV 1/Pre%)呈负相关(P<0.01),而与BALF中的中性粒细胞、巨噬细胞、淋巴细胞计数及IL-13、FGF-2水平呈正相关(P<0.05)。结论TRPC1可能通过参与慢阻肺慢性气道炎症过程促进疾病的发生发展,而ICS在一定程度上可干预该作用。

Influence of TRPC1 on chronic airway inflammation of COPD

Objective To explore the expression levels of transient receptor potential channel C1(TRPC1)in bronchial epithelial cells of chronic obstructive pulmonary disease(COPD)patients and the relationship between TRPC1 and chronic airway inflammation.Methods 78 patients with pulmonary nodule which needed fiberopic bronchoscope for further diagnosis were selected.According to guidelines for diagnosis and treatment of chronic obstructive pulmonary disease,the above patients were divided into the control group(n=32)and the COPD group(n=46).In addition,COPD patients were randomly assigned to 2 subgroups:three times daily budesonide(the ICS group)and three times daily placebo(the non-ICS group).All patients were under bronchoalveolar lavage and protected specimen brush examination,then the TRPC1 in samples of bronchial epithelial cells were measured by Western blot and qRT-PCR and inflammatory cells in bronchoalveolar lavage fluid(BALF)were counted.The levels of IL-13 and FGF-2 in BALF were measured by ELISA.Results The levels of TRPC1 protein and mRNA in the COPD group were higher than those in the control group(P<0.05).Meanwhile,the expressions of TRPC1 protein and mRNA in the ICS subgroup was lower than that in the non-ICS subgroup(P<0.05).On the other hand,compared with the control group,the numbers of macrophages,lymphocytes,neutrophils and the levels of IL-13,FGF-2 in BALF of the COPD group were significantly higher(P<0.05).The counts of macrophages,lymphocytes,neutrophils,eosinophils and the expressions of IL-13 and FGF-2 in the ICS group were lower than those in the non-ICS group(P<0.05).Negative correlation between the expression of TRPC1 protein and mRNA in bronchial epithelial cells and FEV 1/Pre%was found(P<0.01),but the levels of TRPC1 protein and mRNA had a positive correlation with the counts of macrophages,lymphocytes,neutrophils and the expressions of IL-13 and FGF-2 in BALF(P<0.05).Conclusion TRPC1 may play an important role in chronic airway inflammation of COPD patients and ICS could intervene the expression of TRPC1 in bronchial epithelial cells.