视黄酸对大鼠哮喘模型多种炎性因子的影响

目的探讨吸入视黄酸(RA)对急性发作期和慢性持续期哮喘大鼠多种炎症因子影响和作用机制。方法以鸡卵清蛋白(OVA)激发大鼠7d或30 d以制备急性或慢性哮喘模型。在1-7 d或23-30 d期间分别用10μg/ml RA(RA组)、10μg RA+5μg/ml budesonide(RA+BU组)、石蜡油(PO组)雾化吸入治疗1周。急性模型7 d后取血清与肺脏进行检测,慢性模型30 d及随后休息10 d取上清与肺脏进行检测。用免疫荧光、ELISA法检查肺间质细胞因子与血Th因子表达。结果急性发作期PO组胸腺基质淋巴细胞生成素(TSLP)、核因子-κB(NF-κB)、干细胞因子(SCF)表达增加。RA能下调TSLP,但SCF明显上调。慢性持续期PO组TSLP、NF-κB、SCF、IL-4随时间逐步上调,肺感染病灶多,肺泡隔中度增宽。RA组主要炎症因子水平逐渐降低,其中TSLP、IL-4、SCF减少具统计学差异;肺感染病灶少,肺泡隔增宽较轻。BU+RA组下调TSLP表达,但SCF持续上调,肺泡出血与感染较重。结论 RA通过活化巨噬细胞,短暂加重急性发作期哮喘过敏反应,但抑制慢性持续期哮喘肺间质过敏炎症,具免疫调整和抗感染作用。

EFFECT OF RETINOIC ACID ON INFLAMMATORY FACTORS OF ASTHMA IN RAT MODELS

Objective To study the effect of retinoic acid(RA) on many inflammatory factors of asthma in rats and its mechanism.Method The rats were challenged with OVA aerosol for 7d or 30d.10 μg/ml RA(RA group),RA +5 μg/ml of budesonide(RA + BU group) and paraffin oil(PO group) inhalation therapy were performed for 1 w.at the challenged period 1-7 d for model of acute asthma,or 23-30 d for model of chronic asthma respectively.Serum and lung tissue were taken at D 7 for acute model,at D 30 and the day after 10 d rest following D30 respectively.The expression of lung interstitial cytokines and blood Th factors were checked by immunofluorescence assay(IFA) and enzyme-linked immunosorbent assay(ELISA).Results At the onset of acute asthma the thymic stromal lymphopoietin(TSLP),nuclear factor κB(NF-κB),stem cell factors(SCF) expression were increased in PO group.RA down-regulated TSLP,but obviously increased SCF expression.During chronic persistent asthma period,the expression of TSLP,NF-κB,SCF and IL-4 were gradually up-regulated along with time,alveolar septum widened moderately,more infectious foci in lung found in PO group.In RA group,the main inflammatory factors were reduced as TSLP,IL-4 and SCF with statistically significant differences,while only few infectious foci in lung and alveolar septum widened gently.In BU+ RA group,TSLP expression was down-regulated,but SCF still up-regulated with severe alveolar hemorrhage and infection.Conclusion RA increased the allergic reactions temporarily at onset of acute asthma period through activation of macrophages,but had inhibitory effect of chronic interstitial lung allergic inflammation through immune monitoring and anti-inflammation.