β_2-肾上腺素受体表达水平与支气管哮喘气道重塑的关系

Association between expression of β_2-adenergic receptor and bronchial airway remodeling in asthma

目的通过观察β2-肾上腺素受体(β2-adenergic receptor,β2-AR)在支气管哮喘(简称哮喘)模型小鼠气道壁组织表达水平的变化,探讨β2-AR表达水平与气道重塑的关系及观察应用β2-受体激动剂对小鼠气道重塑的影响。方法 30只雌性BALB/c小鼠分为3组,每组10只,分别为对照组(DZ)、哮喘模型组(MX)和特布他林组(TB)。采用0.2%卵清白蛋白(ovalbumin,OVA)溶液腹腔注射致敏及2.5%OVA溶液雾化吸入激发的方法制作小鼠哮喘气道重塑模型,同时给予β2-受体激动剂(特布他林)干预,最后一次激发24h内处死小鼠,取其肺组织,对肺组织切片进行HE染色,以医学图像分析软件测量支气管基底膜周径(Pbm)、总气道壁面积(Wat)和平滑肌面积(Wam),同时采用免疫组织化学法,应用上述图像分析软件检测气道壁组织β2-AR的积分光密度值(IOD)。结果①各组小鼠总气道壁面积/支气管基底膜周径(Wat/Pbm):MX组(25.37±4.25)与DZ组(12.89±1.71)、TB组(15.98±2.58)相比较,气道壁显著增厚(P<0.01),TB组与DZ组相比较,气道壁厚度无明显差别(P>0.05);各组小鼠平滑肌面积/支气管基底膜周径(Wam/Pbm):MX组(7.58±2.16)与DZ组(2.55±0.72)、TB组(3.54±1.63)相比,气道平滑肌增厚(P<0.05),TB组与DZ组相比气道平滑肌厚度无明显差别(P>0.05)。②各组小鼠气道壁β2-AR表达的IOD值:与DZ组(24.90±2.42)相比较,MX组(19.88±1.94)小鼠气道壁组织β2-AR的表达水平显著降低(P<0.01),同时TB组(22.10±1.08)小鼠气道壁组织β2-AR的表达水平也显著低于对照组小鼠(P<0.01)。结论①应用β2-受体激动剂可通过抑制气道平滑肌增殖,减轻小鼠哮喘气道壁增厚,干预气道重塑;②哮喘发生气道重塑时,小鼠气道壁组织β2-AR表达明显下调,同时应用-受体激动剂(特布他林)可下调小鼠气道壁组织-AR的表达。

Objective To study the association of the expression of β2-adenergic receptor in airway and bronchial airway remodeling, and investigate the effects of β2-adrenergic receptor agonist used in early phase on airway remodeling in ovalbumin (OVA) sensitized and challenged mice by observing the expression of β2-adenergic receptor in airway of mice.Methods Thirty BALB/c mice were divided into 3 groups (10 in each group) including group DZ (saline sensitized/challenged mice), group MX (OVA sensitized/challenged mice) and groupTB (OVA sensitized/challenged mice and treated by terbutaline). Mice were sensitized by 0.2% OVA solution and challenged by ultrasonic atomization inhalation of 2.5% OVA solution to establish murine model of asthma characterized by airway remodeling. To assess the effects of β2-adrenergic receptor agonist(terbutaline)on the development of airway remodeling, mice were treated with aerosolized terbutaline. After drawing materials, hematoxylin and eosin (HE) staining were performed.The pathological changes in bronchopulmonary tissue of mice were detected.The basementmembrane perimeter (Pbm), the airwaywall area (Wat) and the smooth musclewall aera (Wam) were measured and calculated by using image analysis system. The concentration of β2-adenergic receptor in broncho-pulmonary tissue was observed by immunohistochemical method and the integral optical density (IOD values) of it was measured.Results ①The airwaywall area /the basementmembrane perimeter (Wat/ Pbm):the Wat/ Pbm of group MX (25.37±4.25) increased significantly when compared with group DZ [(12.89±1.71),P<0.01] and group TB [(15.98±2.58),P<0.01],and there were no significant differences between group TB and group DZ (P>0.05); the smooth muscle wall aera/ the basementmembrane perimeter(Wam/Pbm):the Wam/Pbm of group MX (7.58±2.16) increased when compared with group DZ [(2.55±0.72),P<0.05]and group TB [(3.54±1.63),P<0.05], and there were no significant differences between group TB and group DZ(P>0.05). ②The integral optical density(IOD values) of β2-adenergic receptor in broncho pulmonary tissue:in group MX (19.88±1.94) and group TB (22.10±1.08), the concentration of β2-adenergic receptor decreased, and significantly different from that in group DZ[(24.90±2.42),P<0.01].Conclusions ①In treatment of asthma, β2-adrenergic receptor agonist (terbutaline) may affect the airway remodeling of mice by suppressing smooth muscle proliferation and decreasing the thickness of bronchial wall.②The concentration of β2-adenergic receptor decreased in the airway remodeling in murine model of asthma, and the expression of β2-adenergic receptor in bronchial wall of murine model may be down-regulated by atomization inhales of β2-adrenergic receptor agonist(terbutaline).