Gao Fu-sheng, Gao Yan-yan, Liu Mei-juan, Liu Yong-quan
Department of Respiratory Medicine, the Affiliated Hospital of Weifang Medical College, Weifang 261031, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2012 Jun;35(6):423-8.
To explore the effects of chronic Aspergillus fumigatus (Af) exposure on the expression of mucin 5AC (MUC5AC) in the airways of asthmatic rats.
Fifty-six male Wistar rats were randomly divided into 8 groups: chronic asthma (group A), chronic asthma plus Af spores inhalation for 1 week (group B), 3 weeks (group C) and 5 weeks (group D), chronic asthma plus saline inhalation for 5 weeks (group E), OVA-sensitized and-saline-challenged group (group F) and OVA-sensitized and-saline-challenged plus Af spores inhalation for 5 weeks (group G) (each n = 8). The airway resistance (Raw) and the change rate of Raw after acetylcholine provocation were detected using a computerized system. The level of MUC5AC mRNA in the lung tissue was measured by RT-PCR, and the expression of MUC5AC in airway epithelial cells were demonstrated by immunohistochemistry. The concentration of IL-13 in BALF was measured by ELISA. The extent of goblet cell hyperplasia was evaluated on periodic acid-Schiff stain (PAS) lung sections.
In group B, C, and D, the level of MUC5AC mRNA (MUC5AC mRNA/β-actin mRNA) (1.9 ± 0.4, 2.3 ± 0.6, 2.9 ± 0.8, respectively), the integrated optical density (value A) of MUC5AC positive stain in airway epithelial cells (278 ± 58, 566 ± 64, 891 ± 80, respectively), the concentration of IL-13 in BALF (µg/L) (96 ± 16, 136 ± 22, 197 ± 34, respectively), and the ratio of goblet cell area to epithelial cell area(%) (16 ± 5, 23 ± 7, 36 ± 9, respectively), were higher than those in group A, E, F and G (all P < 0.05). The change rate of Raw(%) in group C and D (61.91 ± 5.26 and 84.69 ± 6.38) were higher than that in group A, E, F and G (all P < 0.05). The level of MUC5AC mRNA and the value A of MUC5AC were positively correlated with the ratio of goblet cell area to epithelial cell area (r = 0.578, P < 0.05;r = 0.614, P < 0.05, respectively) and the change rate of Raw (r = 0.638, P < 0.05;r = 0.564, P < 0.05, respectively) in group B, C and D.
Chronic Aspergillus fumigatus exposure upregulated the expression of MUC5AC in the airway epithelial cells and induced goblet cell hyperplasia, resulting in increased airway hypersensitivity in rats with chronic asthma.
探讨慢性暴露于烟曲霉(Af)对哮喘大鼠气道中黏蛋白5AC(MUC5AC)表达的影响。
56只雄性Wistar大鼠随机分为8组:慢性哮喘组(A组)、慢性哮喘加吸入Af孢子1周组(B组)、3周组(C组)和5周组(D组)、慢性哮喘加吸入生理盐水5周组(E组)、卵清蛋白致敏和生理盐水激发组(F组)以及卵清蛋白致敏和生理盐水激发加吸入Af孢子5周组(G组)(每组n = 8)。使用计算机系统检测气道阻力(Raw)及乙酰胆碱激发后Raw的变化率。采用RT-PCR检测肺组织中MUC5AC mRNA水平,免疫组织化学法检测气道上皮细胞中MUC5AC的表达。通过ELISA检测支气管肺泡灌洗液(BALF)中IL-13的浓度。在过碘酸-希夫染色(PAS)肺切片上评估杯状细胞增生程度。
B组、C组和D组中,MUC5AC mRNA水平(MUC5AC mRNA/β-肌动蛋白mRNA)(分别为1.9±0.4、2.3±0.6、2.9±0.8)、气道上皮细胞中MUC5AC阳性染色的积分光密度(A值)(分别为278±58、566±64、891±80)、BALF中IL-13的浓度(μg/L)(分别为96±16、136±22、197±34)以及杯状细胞面积与上皮细胞面积的比值(%)(分别为16±5、23±7、36±9)均高于A组、E组、F组和G组(均P < 0.05)。C组和D组的Raw变化率(%)(分别为61.91±5.26和84.69±6.38)高于A组、E组、F组和G组(均P < 0.05)。在B组、C组和D组中,MUC5AC mRNA水平和MUC5AC的A值与杯状细胞面积与上皮细胞面积的比值呈正相关(r = 0.578,P < 0.05;r = 0.614,P < 0.05)以及与Raw变化率呈正相关(r = 0.638,P < 0.05;r = 0.564,P < 0.05)。
慢性暴露于烟曲霉可上调哮喘大鼠气道上皮细胞中MUC5AC的表达并诱导杯状细胞增生,导致慢性哮喘大鼠气道高反应性增加。