罗红霉素对哮喘大鼠气道重塑中成肌纤维细胞、TGF-β1和 IFN-γ的影响

目的: 探讨成肌纤维细胞(myofibroblast,MF) 、转化生长因子β₁ (transforming growth factor-beta 1, TGF-β₁ ) 和 IFN-γ在哮喘气道重塑中的作用,并观察罗红霉素对哮喘气道重塑的影响。方法: SD大鼠 30 只, 随机分为哮喘组、生理盐水对照组、罗红霉素治疗组, 每组 10 只。利用卵白蛋白(ovalbumin,OVA)/Al(OH)₃ 致敏与 OVA 雾化吸入激发建立大鼠哮喘模型。免疫组化测定支气管上皮下成肌纤维细胞的 α-平滑肌肌动蛋白(α-smoothmuscle actin, α-SMA) 表达含量, 并使用图像分析技术进行积分吸光度(integral optical density, IOD) 定量分析测定 。ELISA 法测定支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF) 中 TGF-β₁ 和IFN-γ的浓度。结果: 定量分析测定的 IOD 值显示哮喘组支气管上皮下成肌纤维细胞 α-SMA 表达含量较生理盐水对照组增加(P<0.01) , 罗红霉素治疗组表达含量较哮喘组减少(P<0.05) 。ELISA 法测定哮喘组 BALF 中 TGF-β₁ 浓度较对照组升高(P<0.01) , 治疗组较哮喘组浓度降低(P<0.01) , 但仍高于对照组(P<0.05) 。哮喘组BALF 中 IFN-γ浓度较对照组降低(P<0.01) , 治疗组较哮喘组浓度高(P<0.01) , 但仍低于对照组(P<0.05) 。结论: 成肌纤维细胞在气道重塑中起重要作用。罗红霉素可能通过减少 TGF-β₁ ,增加 IFN-γ的产生, 从而抑制成肌纤维细胞增殖和表达, 起到抗哮喘气道重塑作用 。

Effects of roxithromycin on myofibroblast,TGF-β1 and IFN-γin rats asthma airway remodeling

AIM: To explore the effects of myofi-broblast, TGF-β₁ and IFN-γon asthma airwy remodel-ing and observe the influence of roxithromycin on asth-ma airway remodeling .METHODS: In the experi-ment, thirty SD rats were randomly divided into the asthma group(group A, n =10) , the sodium chloride control group (group C, n =10) and the roxithromycin group(group R, n =10) .The rats were sensitized and stimulated with ovalbumin/Al(OH)3 and OVA atomiza-tion inhalation respectively to establish the asthma mod-el.The α-smooth muscle actin(α-SMA) expression of tracheal subepithelium myofibroblast were determined by immunohistochemistry .The integral optical density (IOD) were quantitatively analysed by image analysis technique .The concentration of TGF-β₁ and IFN-γin bronchoalveolar lavage fluid(BALF) were measured by ELISA .RESULTS: The IOD value suggested that the α-SMA expression of tracheal subepithelium myofibro-blast were increased compared with group C (P<0.01) , and the expression in group R were decreased comparedwith group A (P<0.05) .The expression of TGF-β₁ in BALF in groupA were increased than that in group C(P<0.01) , and TGF-β₁ expression in group R were decreased than that in group A(P<0.01) , but were still higher than that in group C(P<0.05) .The expressions of IFN-γin BALF in group A were de-creased than that in group C(P<0.01) , and IFN-γ expression in group Rwere increased than that in group A(P<0.01) , but were still lower than that in group C(P<0.05) .CONCLUSION: Myofibroblast plays an important role during airway remodeling .Roxithro-mycin may decrease the expressions of TGF-β₁ and in-crease the expressions of IFN-γ that inhibits the prolif-eration and expression of myofibroblast .So roxithromy-cin may be effective drugs in inhibitting asthma airway remodeling.