成肌纤维细胞在哮喘气道重塑中的作用及地塞米松对其的影响

成肌纤维细胞在哮喘气道重塑中的作用

及地塞米松对其的影响

（作者： _________ 单位：___________ 邮编：___________ ）

作者：林洁，戴元荣，赵初环，徐永安，吴成云，颜孙舜

【摘要】目的：探讨成肌纤维细胞（MF）在哮喘气道重塑中的作用并观察地塞米松对其的影响。方法：SD大鼠30只，随机分为哮喘组（A 组）、生理盐水对照组（C组）和地塞米松治疗组（D组），每组10只。利用卵白蛋白（OVA）/AI（OH）3致敏与OVA雾化吸入激发建立大鼠哮喘模型。免疫组化测定肺组织中支气管上皮下成肌纤维细胞的a -平滑肌肌动蛋白（a-SMA）表达含量，并使用图像分析技术进行积分光密度（IOD ）定量分析测定。ELISA法测定支气管肺泡灌洗液（BALF ）中TGF- （31和IFN- Y的浓度。结果：①定量分析测定的IOD值显示A 组支气管上皮下MF的a-SMA表达量较C组显著增加（P V 0.01 ），D 组表达量较A组减少（P V0.05 ）。②ELISA法测定结果：A组BALF 中TGF- 31浓度较C组显著升高（P V 0.01 ），D组较A组浓度降低

（P V 0.01 ），但仍高于C组（P V 0.05 ）。A组BALF中IFN-丫浓

度较C组显著降低(P V 0.01 ), D组较A组浓度高(P V 0.01)，但仍低于C组(P V 0.05 )。结论：MF在气道重塑形成中起重要作用。地塞米松可能通过减少TGF- (31，增加IFN- 丫的产生，抑制MF增殖和表达，起到抗哮喘气道重塑的作用。

【关键词】哮喘；气道重塑；成肌纤维细胞；糖皮质激素；大鼠Abstract: Objective: To explore the effect of myofibroblast(MF) on asthmatic airway remodeli ng and the effect of dexamethas one on it. Methods: In the experiment ，thirty Sprague-Dawley (SD) rats were randomly divided into the asthma group (group A)，the sodium chloride control group (group C) and the dexamethasone group (group D) . There were ten rats in each group. The rats were sen sitized with ovalbu min and AI(OH)3 before repeatedly exposed to aerosolized ovalbumin. The a-smooth muscle actin (a-SMA) expressions of MF of bronchial subepithelium in lung tissue were assessed with immuno histochemistry.

By image an alysis technique，their integral optical density (IOD) were quantitatively analysed. The concentra-tion of TGF- 3 1 and IFN- 丫in bronchoalveolar lavage fluid (BALF) was measured by ELISA. Results: ①Compared with group C ，the IOD value by quantitative analysis showed that the expression of MF' a-SMA in bronchial subepithelium in group A was sig ni fica ntly in creased ( P V 0.01 )，and the expression in group D was significantly decreased compared

with group A (P 0.05).②The results of ELISA: The concentration of TGF- ［31 in BALF in group A was higher than that in group C (P v

0.01 ), and the concentration of TGF- 31 in BALF in group D was lower than that in group A (P 0.01 ), but still higher than that in group C (P

0.05 ) . The concentration of IFN- 丫in BALF in group A was lower than that in group C (P v 0.01), and the concentration of IFN- 丫in BALF in group D was higher than that in group A(P 0.01) , but still lower than that in group C (P 0.05). Conclusion: MF plays an important role in the course of airway remodeling. Dexamethasone may decrease the

concentration of TGF- 31 and in crease the concen trati on of IFN- 丫，the n in hibit proliferati on and expressi on of MF. So Dexamethas one may be an effective drug to in hibit asthmatic airway remodeli ng.

Key words: asthma ; airway remodeling ; myofibroblast ; glucocorticoids ; rat

大量研究证明，支气管哮喘不仅存在着气道炎症，而且还发生气道

结构的改变，即气道重塑(airway remodel in g)。气道重塑并非只发生在重症哮喘或哮喘病程的晚期，有证据表明在儿童哮喘的早期就存在气道重塑［1，2］。近几年来，有关哮喘气道重塑的研究在国内外已成为一个热点课题。但到目前为止，其发生机制仍未完全阐明，也缺乏有效的防治措施。本研究建立大鼠哮喘模型，探讨成肌纤维细胞(myofibroblast, MF)在哮喘气道重塑中的作用并观察地塞米松对其的

影响

1材料和方法

1.1实验动物SPF级健康雄性SD大鼠30只，体重150〜200 g , SCXK(浙)2005-0019。

1.2主要试剂和设备卵白蛋白(OVA)，购自美国Sigma公司；