支气管哮喘大鼠肺内Th1/Th2失衡及雾化吸入地塞米松的影响

The imbalance of Th1/Th2 cytokine expressions in lungs of asthmatic rats and the effect of dexamethasone on these cytokines

目的观察支气管哮喘大鼠肺组织内T辅助细胞两个亚群(Th1/Th2)的功能状态及地塞米松对其的影响。方法通过卵白蛋白腹腔注射与雾化吸入建立大鼠哮喘模型,并分为哮喘组(A组)、雾化吸入地塞米松组(B组)、正常对照组(C组)。采用逆转录-聚合酶链反应(RT-PCR)技术检测地塞米松对哮喘大鼠肺组织IL-4、IL-5以及IFN-γ的mRNA表达的影响,并用光镜观察肺组织支气管壁厚度(WA/Pi)、支气管平滑肌厚度(SMC-A/Pi)及支气管黏膜及黏膜下嗜酸粒细胞(Eos)、淋巴细胞(L)、中性粒细胞(Neu)数量。结果A组肺组织中IL-4、IL-5的mRNA表达及WA/Pi、SMC-A/Pi、支气管黏膜及黏膜下Eos、L、Neu浸润程度显著高于C组(均P<0.001),但在B组中表达降低、浸润程度减轻(与A组相比,P<0.001);B组与C组比较差异也有显著性。A组肺组织中IFN-γ的mRNA表达低于C组(P<0.001),B组与A组比较,IFN-γ的mRNA表达无显著性差异(P>0.05)。肺组织内IL-4、IL-5mRNA的表达与WA/Pi、SMC-A/Pi的改变以及Eos、L、Neu的浸润呈正相关(P均<0.05),IFN-γ的mRNA表达与上述改变以及Eos、L、Neu的浸润呈负相关(P均<0.05)。结论支气管哮喘大鼠存在Th1/Th2失衡;地塞米松主要通过降低哮喘大鼠肺组织中Th2类细胞因子IL-4和IL-5的基因转录,发挥其抗气道重塑和气道炎症的作用。

Objective: To observe the state of Th1/Th2 cytokine expressions in lungs from asthmatic rats and the effect of dexamethasone on it. Methods: An animal model of asthma was established by OVA sensitizing challenge to SD rats. The rats were devided into asthma group (group A), dexamethasone aerosol inhalation group (group B) and normal control group (group C). Dexamethasone aerosol inhalation was given 1 h before each OVA challenge. The mRNA expressions of the cytokines IL 4,IL 5,IFN γ were analyzed by RT PCR, the airway wall thickness(WA/Pi) and the airway smooth muscle thickness(SMC A/Pi) were measured and the numbers of eosinophils,lymphocytes and neutrophils in the bronchial mucosa and submucosa were counted with microscope. Results: The mRNA expressions of the cytokines IL 4 and IL 5, the WA/Pi,the SMC A/Pi and the infiltration extent of eosinophils, lymphocytes and neutrophils in airway mucosa and submucosa were higher in group A than in group C (all P <0.001), but were significantly decreased in group B as compared with group A ( P <0.001). They were also significantly different between groups B and C.The mRNA expression of the cytokine IFN γ was lower in groups A than in group C ( P <0.001), but there was no significant difference between group A and group B ( P >0.05). The correlation analysis showed that the mRNA expressions of the cytokines IL 4 and IL 5 in lungs had significantly positive correlation with the values of the WA/Pi,the SMC A/Pi and the infiltration extent of eosinophils, lymphocytes and neutrophils (all P <0.05), but the mRNA expression of the cytokine IFN γ had negative correlation with these parameters (all P <0.05). Conclusion: There is an imbalance between Th1 and Th2 in asthmatic rats. Dexamethasone shows its effect of relieving asthmatic symptoms and preventing airway remodeling by marked inhibition of the mRNA expressions of Th2 type cytokines IL 4,IL 5. [