地塞米松对哮喘大鼠Th1/Th2失衡及嗜酸细胞fas、bcl-2 mRNA表达的影响

Effects of dexamethasone on Th1/Th2 imbalance and expression of fas,bcl-2 mRNA in eosinophils in rat model of asthma

目的 :观察地塞米松 (DXM)对哮喘大鼠Th1/Th2失衡以及嗜酸细胞 (EOS)fas、bcl 2mRNA表达的影响 ,探讨糖皮质激素治疗哮喘气道炎症的作用机制。方法 :清洁级雄性SD大鼠 30只 ,随机分为 3组 :正常对照组 (C) ,哮喘组 (A) ,地塞米松治疗组 (T) ,每组 10只。采用卵清白蛋白制作大鼠哮喘模型。用夹心酶联免疫吸附试验 (sandwichELISA)法检测血浆及支气管肺泡灌洗液 (BALF)中IL 4、IFN γ的水平 ;用原位杂交法检测fas和bcl 2mRNA在气道壁EOS上的表达。结果 :A组大鼠IFN γ表达水平较C组明显下调 (P <0 .0 1) ,同时IL 4表达水平则有明显上调 (P <0 .0 1) ,表现出明显的Th1/Th2失衡。fasmRNA的表达在A组明显下降(P <0 .0 1) ,bcl 2mRNA的表达则有明显上调 (P <0 .0 1)。地塞米松治疗在纠正A组大鼠Th1/Th2失衡的同时可上调fasmRNA的表达 ,下调bcl 2mRNA的表达。结论 :纠正哮喘大鼠Th1/Th2失衡 ,调节EOSfas、bcl 2mRNA的表达是地塞米松减轻哮喘气道炎症的可能机制之一。

Objective:To observe the effects of dexamethasone(DXM) on Th1/Th2 balance and fas,bcl-2 mRNA expression in eosinophil of asthmatic rats and to explore mechanisms of steroid in treating the infectious airway of asthmatics.Methods:Thirty Sprague-Dawley(SD) rats were randomly divided into 3 groups:normal rats(C),asthmatic rats(A),dexamethasone treated rats(T). Asthmatic rats were sensitized intraperitioneally and challenged nebulizedly with ovalbumin(OVA). The animals were sacrificed 24 hours after the last challenge. The assessment of IL-4,IFN-γ in both serum and bronchoalveolar lavage fluid(BAL) was performed. In addition,mRNA expression of Bcl-2 and Fas in eosinophils presenting in airway were evaluated.Results:As it had been expected,there was a distinct imbalance of Th1/Th2 in group A. The productions of IL-4 both in serum or in BAL fluid in group A were increased significantly from the baseline (P<0.01),and IFN-γ production in BALF was lowered greatly(P<0.01). Dexamethasone treatment could significantly reduce the production of IL-4 in both serum and BALF(P<0.01),meanwhile dexamethasone could also upregulate the IFN-γ production in 24 hours after the last antigen challenge in group A,the mRNA expression of bcl-2 and fas in eosinophils presenting in airway were significantly increased or decreased respectively(P<0.01). The expression of fas was raised and that of bcl-2 was lowered after DXM treatment.Conclusion:To correct a distinct imbalance of Th1/Th2 in asthmatic rat and adjust fas mRNA expression may be one of the mechanisms that DXM alleviates airway inflammation in asthma.