罗格列酮对大鼠气道黏液高分泌的影响

Influence of rosiglitazone on mucus hypersecretion in rat airway epithelium

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对丙烯醛所致大鼠气道黏液高分泌的影响及其机制。方法将36只雄性SD大鼠随机分为6组,即对照组(A组)、罗格列酮自身对照组(B组)、模型组(C组)、低剂量罗格列酮组(D组)、中剂量罗格列酮组(E组)和高剂量罗格列酮组(F组)。采用酶联免疫吸附测定(ELISA)法检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-8浓度。分别用阿辛蓝-过碘酸雪夫(AB-PAS)和免疫组化染色检测气道黏蛋白和MUC5AC的表达。结果丙烯醛吸入各组BALF中TNF-α、IL-1β和IL-8浓度,以及气道黏蛋白、MUC5AC表达与A组比较明显增加(P<0·01,P<0·05),TNF-α、IL-1β、IL-8浓度与黏蛋白、MUC5AC表达分别呈正相关(r分别为0·827,0·795,0·924,0·805,0·812和0·917;P<0·01或P<0·05)。给予低、中、高剂量罗格列酮治疗后,D组、E组和F组BALF中TNF-α和IL-8浓度,以及气道黏蛋白和MUC5AC表达均逐渐降低,其中E、F组与C、D组比较,F组与E组比较,差异均有统计学意义(P<0·01或P<0·05)。结论罗格列酮能够下调TNF-α和IL-8的表达,减轻气道黏液高分泌。

Objective To investigate the influence and mechanism of rosiglitazone, an agonist of peroxisome proliferators activated receptor gamma（PPAR-γ）, on mucus hypersecretion in rat airway. Methods 36 male SD rats were randomly divided into 6 groups, ie. a control group（ group A）, a rosiglitazone group（ group B） ,a mucus hypersecretion group（group C）, a low dosage group of rosiglitazone（ group D）, a moderate dosage group of rosiglitazone（group E）, a high dosage group of rosiglitazone（ group F）. The levels of tumor necrosis factor-α（TNF-α）, interleukin-1β （IL-1β） and IL-8 in bronchoalveolar lavage fluid （BALF） were detected by ELISA. The expressions of MUC5AC and mucin in bronchial tissues were examined by histochemical analysis and alcian blue-periodic acid schiff（AB-PAS） staining, respectively. Results The overexpressions of MUC5AC, mucin and the increased levels of TNF-α, IL-1β, IL-8 were detected in groups C,D,E and F compared to group A （P 〈 0.01 or P 〈 0.05）. In groups D, E and F, the expressions of MUC5AC, mucin and the levels of TNF-α, IL-1β, IL-8 were gradually decreased（ P 〈 0.01 or P 〈 0.05）. The decreases were obvious in groups E and F compared to group C. The increased levels of TNF-α, IL-1β, and IL-8 in BALF were well correlated with the overexpression of MUC5AC and mucin （ r = 0. 827, 0. 795, 0. 924, 0. 805, 0. 812, 0. 917, respectively, P 〈 0.01 or P 〈 0.05） in the mucus hypersecretion group. Conclusion Rosiglitazone can decrease the expressions of TNF-α, IL-8 and suppress mucus hypersecretion in rat airway.