肺表面活性物质在哮喘大鼠气道重塑中的作用及机制

Therapeutic effect of pulmonary surfactant on airway remodeling in rats with allergic asthma

目的:研究肺表面活性物质(pulmonarysurfactant,PS)对哮喘大鼠气道重塑的治疗作用并探讨其可能机制.方法:实验分3组:正常对照组(20只)、哮喘对照组(20只)和PS治疗组(20只),取肺组织与不同刺激因素作用后做组织切片,图像分析方法测定气道壁、气道平滑肌厚度及平滑肌细胞数,并计算平滑肌收缩百分比(PMS);免疫组织化学方法检测表皮生长因子(EGF)在各组大鼠小气道中的表达.结果:①PS治疗组的气道重塑程度显著低于哮喘组,与对照组比较无差异.②哮喘组气道平滑肌对腺苷的反应性(以PMS表示)较对照组增加24%,PS治疗组与哮喘组比较,PMS下降15%;哮喘组气道平滑肌对乙酰胆碱的反应性较对照组增加25%,PS治疗组与哮喘组比较,PMS下降16%.③哮喘组EGF的表达较对照组明显增加(P<0.01),PS治疗组EGF的表达较哮喘组明显减少(P<0.01).结论:外源性PS可以有效减轻哮喘大鼠气道重塑的程度,这可能与抑制EGF的合成及释放有关.

AIM: To study the therapeutic effect of pulmonary surfactant (PS) on airway remodeling in rats with allergic asthma and to investigate the possible mechanism. METHODS: Sixty rats were randomly divided into three groups: control (20), asthmatic (20) and therapeutic group (20). After incubating with different stimulus, lung tissue sections were stained with HE. The airway internal perimeter, wall area, external perimeter were measured by image analysis system and percentage of muscle shortening (PMS) was calculated. The expression and distribution of endothelium growth factor (EGF) in small airway of rats were detected using immunohistochemistry technique. RESULTS: ① The degree of airway remodeling in therapeutic group decreased significantly than that in asthmatic group, but compared with control group it was not statistically significant. ② Responsiveness of airway smooth muscle to adenosine (represented by PMS) in asthmatic group increased 24% compared with that in control group, but PMS decreased 15% in therapeutic group compared with that in asthmatic group. PMS to acetylcholine in asthmatic group increased 25% compared with that in control group, but PMS decreased 16% in therapeutic group compared with that in asthmatic group. ③ In the asthmatic group, the expression and distribution of EGF increased significantly than that in controls (P<0.01), but decreased significantly in therapeutic group compared with that in asthmatic group (P<0.01). CONCLUSION: Exogenous PS can effectively prevent airway remodeling in rats with allergic asthma, possibly by downregulating the synthesis and release of EGF.