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.
关键词
15-脂氧合酶 /
支气管哮喘 /
炎症 /
地塞米松 /
大鼠
Key words
15-lipoxygenase /
Asthma /
Inflammation /
Dexamethasone /
Rats
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］Kleinman R, Mura M, Liu MY. 半胱氨酰白三烯拮抗剂治疗儿童哮喘［J］. 中国当代儿科杂志，2005，7(5): 398-403.
［2］Tremblay K, Daley D, Chamberland A, Lemire M, Montpetit A, Laviolette M, et al. Genetic variation in immune signaling genes differentially expressed in asthmatic lung tissues［J］. J Allergy Clin Immunol, 2008, 122(3): 529-536.
［3］苏苗赏，李昌崇，林立，郑吉善，郑仰明，管小俊，等. 地塞米松对年幼期哮喘大鼠 Toll 样受体 4 信号转导的调节机制［J］. 中华儿科杂志，2006，44(12): 937-940.
［4］Kühn H, O′Donnell VB. Inflammation and immune regulation by 12/15-lipoxygenases［J］. Prog Lipid Res, 2006, 45(4): 334-356.
［5］Levy BD. Lipoxins and lipoxin analogs in asthma［J］. Prostaglandins Leukot Essent Fatty Acids, 2005, 73(3-4): 231-237.
［6］Bannenberg GL, Aliberti J, Hong S, Sher A, Serhan C. Exogenous pathogen and plant 15-lipoxygenase initiate endogenous lipoxin A4 biosynthesis［J］. J Exp Med, 2004, 199(4): 515-523.
［7］Hashimoto A, Murakami Y, Kitasato H, Hayashi I, Endo H. Glucocorticoids cointeract with lipoxin A4 via lipoxin A4 receptor (ALX) upregulation［J］. Biomed Pharmacother, 2007, 61(1): 81-85.
［8］Celik GE, Erkekol FO, Misirligil Z, Melli M.Lipoxin A4 levels in asthma: relation with disease severity and aspirin sensitivity［J］. Clin Exp Allergy, 2007, 37(10): 1494-1501.
［9］Fierro IM, Serhan CN. Mechanisms in antiinflammation and resolution: the role of lipoxins and aspirin triggered lipoxins［J］. Braz J Med Biol Res, 2001, 34(5): 555.
［10］Chu HW, Balzar S, Westcott JY, Trudeau JB, Sun Y, Conrad DJ, et al. Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition［J］. Clin Exp Allergy, 2002, 32(11): 1558-1565.
［11］Profita M, Sala A, Riccobono L, Paternò A, Mirabella A, Bonanno A, et al. 15-Lipoxygenase expression and 15(S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects［J］. J Allergy Clin Immunol, 2000, 105(4): 711-716.
PDF(1288 KB)
