地塞米松对急性哮喘大鼠肺组织15-脂氧合酶表达的影响

Effects of dexamethasone on 15-lipoxygenase expression in lungs of asthmatic rats

摘要:

目的：15-脂氧合酶（15-LO）是一种表达于哮喘肺组织，参与抗炎和促炎物质生成的过氧化物酶。基因队列研究认为它可能对过敏性哮喘起保护作用。本研究通过观察哮喘大鼠肺组织 15-LO 的表达以及地塞米松对其表达的影响，探讨15-LO在哮喘中的作用。方法：将 27 只雄性 Sprague-Dawley 大鼠随机分为：正常对照组、哮喘组、地塞米松组。采用卵清白蛋白（OVA）致敏、激发，建立支气管哮喘大鼠气道炎症模型。ELISA 法测定肺组织匀浆 15-LO 蛋白含量；RT-PCR 法检测肺组织 15-LO mRNA 表达水平。结果：哮喘组大鼠肺组织匀浆 15-LO 蛋白含量（2080±73 μg/mL）及肺组织 15-LO mRNA 转录水平（0.51±0.14）均显著低于正常对照组的（2472±106 μg/mL）和（0.76±0.15）（P<0.01）；地塞米松干预后 15-LO 蛋白（2562±218 μg/mL）及mRNA（1.02±0.34 ）表达均上调（P<0.01）。结论：哮喘大鼠肺组织 15-LO 表达低下，地塞米松可能部分通过上调哮喘大鼠肺组织 15-LO 而发挥抗炎作用。

Abstract:

OBJECTIVE: 15-lipoxygenase (15-LO) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Gene expression profiling studies show the association between 15-LO and allergic asthma. This study was designed to observe the expression of 15-LO in lungs of asthmatic rats and examine the effects of dexamethasone on 15-lipoxygenase expression. METHODS: Twenty-seven male Sprague-Dawley (SD) rats were randomly divided into three groups: control, asthma and dexamethasone (DXM) intervention. An asthma model was prepared by sensitization and challenging with ovalbumin. The production of 15-LO in lung tissue homogenates was measured using ELISA.The expression of 15-LO mRNA in lungs was determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The levels of 15-LO mRNA and protein in the asthma group (0.51±0.14 and 2080±73 μg/mL, respectively) were lower than those in the control group (0.76±0.15 and 2472±106 μg/mL, respectively; P<0.01). DXM intervention increased significantly the levels of 15-LO mRNA and protein (1.02±0.34 and 2562±218 μg/mL) compared with the asthma group (P<0.01). CONCLUSIONS: The production of 15-LO in lung tissues is reduced in asthmatic rats. DXM can increase the expression of 15-LO in lung tissues and thus might provide anti-inflammatory effects in asthmatic rats.