糖皮质激素和抗胆碱能药物对慢性阻塞性肺疾病大鼠模型肺组织腺苷A1受体表达的影响

Expression of adenosine receptor A1 in the rats model of chronic obstructive pulmonary disease could be suppressed by inhaled corticosteroid and anticholinergic agents

目的研究腺苷A1受体在慢性阻塞性肺疾病(COPD)大鼠模型肺组织内的表达水平,旨在探讨腺苷在COPD中的作用及吸入糖皮质激素和抗胆碱能药对其的影响。方法单纯烟熏法建立COPD动物模型。将30只大鼠分为4组:正常对照组、COPD组、布地奈德组及异丙托溴铵组。计数支气管肺泡灌洗液(BALF)中细胞总数及中性粒细胞,逆转录多聚酶链反应(RTPCR)方法测定肺组织腺苷受体mRNA表达,观察布地奈德和异丙托溴铵对腺苷受体表达的影响。结果COPD组BALF白细胞总数和中性粒细胞数显著高于干预组和正常对照组(P<0.01);布地奈德组与异丙托溴铵组BALF细胞总数及中性粒细胞数高于对照组,有显著性差异(P<0.05);两干预组之间比较无显著性差异(P>0.05)。COPD组腺苷A1受体mRNA表达明显高于干预组和对照组,有显著性差异(P<0.05);布地奈德组和异丙托溴铵组腺苷A1受体mRNA表达显著高于对照组,两干预组之间比较无显著性差异(P>0.05)。各组BALF中性粒细胞计数和腺苷A1受体mRNA表达水平有相关性(P<0.05)。结论COPD模型大鼠存在以中性粒细胞为主的气道炎症,肺组织腺苷A1受体mRNA表达与气道炎症呈正相关。推测腺苷参与慢性支气管炎与肺气肿气道炎症形成。吸入激素可使腺苷A1受体mRNA表达下调并可抑制气道炎症,但不能恢复至正常水平。吸入抗胆碱药亦可下调腺苷A1受体mRNA表达,但机制不明。

Objective To investigate the expression of adenosine receptor A1 in pulmonary tissue of the rats model of ehronie obstruetive pulmonary disease （COPD,pathologically,chmnic bronchitis and emphysema ） and observe （he effects of inhaled cortieosteroid or antieholinergie agent on its expression in order to explore the role of adenosine and its receptor in the pathogcnesis of COPD.Methods A rat model of COPD was established by tobacco smoke inhalation. Thirty SD rats were randomly divided into control group, COPD group, COPD with inhaled cortieosteroid （Bndesonide, BUD） group and COPD with inhaled anticholinergic agent ipratropium bromide （IAP）. The total number of cells and the percentages of polymorphonuelear leukocyte（PMN） in bronehoalveolar lavage fluid （BALV） were counted. RT-PCR was used to determine the expression level of AIAR in lung tissue. Results The percentages of PMN in BALF in COPD were increased significantly than those in BUD and lAP intervention group and control group（ P 〈 0.01 ）,The percentages were still elevated in BUD and lAP intervention groups compared to those in control group,but no difference was found between BUD group anti lAP group.The expression level of AI AR in pulmonary tissue in COPD was higher than those in BUD and IAP intervention groups as well as in eontrot group（ P 〈 0.05 ）, while the expression level of A1AR in two intervention groups was not difterent significantly （ P 〉 0. 05 ）. Conclusions In the rat model of COPD the pereerntage ofPMN in BALF and the expression level of AI AR in pulmonary tissue were increased significantly meanwhile a positive correlation between PMN counts and A IAR expression was exhit）ited, suggesting a role of adenosine in the airway inflammation contributing to COPD. Adenosine and its receptor are supposed to be a new target for treatmen uf COPD. Corticosteroid arid antieholinergic agent exhibit potency to suppress A1 AR expression but the underlying mechanism needs further investigation.