过氧化物酶体增殖体活化受体-γ对哮喘小鼠气道黏液的影响

目的:选用罗格列酮作为过氧化物酶体增殖体活化受体γ(PPARγ)的激动剂,探讨PPARγ对哮喘小鼠气道炎症和黏液的影响。方法:动物随机分为正常对照组、哮喘模型组和罗格列酮组,采用鸡卵清蛋白(Ova)致敏和激发制备小鼠哮喘模型。罗格列酮组予罗格列酮3mg·kg-1·d-1灌胃,对照组和模型组用同体积生理盐水代替。检测气管血管周围嗜酸粒细胞(Eos)数目、气管上皮杯状细胞增生指数和黏液储备指数、肺组织MUC5acmRNA的表达及MUC5ac蛋白的表达。结果:罗格列酮组气管血管周围Eos数目(169±s110)个·mm-2显著减少,气道杯状细胞增生指数及黏蛋白MUC5acmRNA的吸光度值分别为(25±16)个·mm-1,(0.83±0.06),和模型组比较差异有显著意义(P<0.05),黏液储备指数为(12±10)%,和模型组比较也有下降,但差异无显著意义。免疫组化显示罗格列酮组的MUC5ac阳性染色程度和正常对照组相似,和模型组比较阳性程度明显减轻。结论:PPARγ抑制哮喘小鼠气道Eos浸润和黏液高分泌。

Effects of peroxisome proliferator-activated receptor gamma on airway mucus production in a murine model of asthma

AIM: Peroxisome proliferator-activated receptor gamma (PPAR-γ), a member of the nuclear hormone receptor superfamily, has been shown to play an important role in the control of inflammatory responses. The aim is to assess the anti-inflammatory potential of rosiglitazone, a PPAR-γ agonist. METHODS: Mice were randomized into three groups: control group, asthma model group and rosiglitazone group. We used a murine model of asthma induced by sensitization and airway challenge with ovalbumin. Rosiglitazone (3 mg·kg -1·d -1) was administered at the time of antigen challenge to rosiglitazone group, while the same dose of normal saline was administered to the other group. Eosinophil(Eos) count, goblet cell hyperplasia ratio (HR), epithelial cell mucus occupying ratio (MOR), mRNA expression of MUC5ac and protein expression of MUC5ac were tested. RESULTS: There were significant differences of Eos count (169±110 vs 942±592), HR (25±16 vs 54±24) and mRNA expression of MUC5ac (12±10) % vs (16±11) % between rosiglitazone group and asthma model group (P<0.05). The MOR of rosiglitazone group (12±10) % was lower than asthma model group, but there were no significant differences (P> 0.05). Protein expression of MUC5ac reduced in rosiglitazone group compare with asthma model group, and similar to control group. CONCLUSION: The results demonstrate that PPAR-γ could inhibit airway eosinophilia and mucus overproduction, and rosiglitazone might have therapeutic potential for airway asthmatic inflammation.