全反视黄酸对哮喘大鼠气道反应性和气道重塑的影响

Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma

目的观察全反视黄酸(ATRA)对哮喘大鼠气道反应性、气道重塑和肺组织基质金属蛋白酶-9(MMP-9)表达的影响。方法 40只大鼠随机分为5组,每组8只:盐水组、模型组、ATRA组、棉籽油组和布地奈德(BUD)组。后4组经卵清蛋白(OVA)致敏14 d后激发6周,构建大鼠慢性哮喘模型。ATRA组、棉籽油组和BUD组每次激发前分别给予ATRA 50μg/kg、棉籽油1 mL和BUD 0.32 mg/kg。5组大鼠行气道反应性检测,并测定肺组织MMP-9表达和气道重塑情况。结果 ATRA干预组的气道反应性与盐水组比较差异无统计学意义(P>0.05),MMP-9表达高于盐水组,差异具有统计学意义(P<0.05)。ATRA干预组的气道反应性和MMP-9表达均明显低于模型组,气道重塑改变减轻,差异具有统计学意义(P<0.05)。结论早期预防性ATRA干预通过减少肺组织MMP-9表达,可在一定程度上减轻哮喘大鼠的气道重塑和气道高反应性。

Objective To study the effects of all-trans retinoic acid（ATRA） on airway responsiveness,airway remodeling and expression of matrix metalloproteinas-9（MMP-9） protein in rats with asthma.Methods Forty rats were randomly divided into five groups： asthma model,normal saline（control）,ATRA treatment,cotton oil treatment and budesonide treatment（n=8 each）.Asthma was induced by ovalbumin sensitization and challenge in the asthma model,and the ATRA,cotton oil or budesonide treatment groups.ATRA（50 μg/kg）,cotton oil（1 mL） or budesonide（0.32 mg/kg） was administered before ovalbumin challenge in the three treatment groups.Airway responsiveness was assessed.The lung tissues were sampled to detect airway remodeling and the expression of MMP-9 protein by immunohistochemistry.Results The expression of MMP-9 in lung tissues in the ATRA treatment group was significantly higher than that in the control group,but the airway responsiveness in the ATRA treatment group was not significantly different from that in the control group.The airway responsiveness and the expression of MMP-9 in lung tissues were significantly reduced in the ATRA treatment group compared with the asthma model group.The airway remodeling was significantly improved in the ATRA treatment group compared with the asthma model group.Conclusions ATRA may alleviate airway hyperresponsiveness and airway remodeling possibly through decreasing the protein expression of MMP-9 in rats with asthma.