目的 观察热休克蛋白(HSP)70/CD80嵌合DNA疫苗对慢性哮喘小鼠气道重塑病理学改变的影响.方法 经肌肉注射HSP70/CD80 DNA疫苗后,雌性健康BALB/c小鼠采用鸡卵清蛋白建立慢性哮喘小鼠模型.全身体积描记仪检测小鼠气道反应性.苏木素-伊红(HE)染色、过碘雪夫酸(PAS)染色、马氏(Masson)三色染色和免疫组化增殖细胞核抗原(PCNA)染色观察肺组织气道重塑病理学改变情况.酶联免疫吸附测定(ELISA)检测支气管肺泡灌洗液中细胞因子γ-干扰素(IFN-γ)和白细胞介素-4(IL-4)含量.实时荧光定聚合酶链反应(PCR)测定脾脏组织IFN-γ和IL-4基因表达水平.结果 与对照组比较,慢性哮喘组小鼠表现为明显的气道高反应性(P<0.05)和气道壁增厚(P<0.05)等气道重塑改变.与慢性哮喘组比较,疫苗组小鼠气道反应性降低(P<0.05),气道重塑减轻;且疫苗组小鼠细胞因子IFN-γ/IL-4比值升高(P<0.05),脾脏组织IFN-γ/IL-4基因表达量比值升高(P<0.05).结论 HSP70/CD80 DNA疫苗对慢性哮喘气道重塑存在抑制作用,表现为延缓气道病理学改变,降低气道阻力.其机制可能与促进IFN-γ的生成,增强Th1型免疫反应,恢复Th1/Th2平衡有关.%Objective To investigate the influence of HSP70/CD80 DNA vaccine on airway remodeling in chronic asthmatic mice. Methods Alter immunized by intramuscular injection with HSP70/CD80 DNA vaccine, the female healthy BALB/c mice were induced to airway remodeling by ovalbumin. Airway hyperresponsiveness (AHR) were measured. Lung tissue sections were stained with hematoxylin and eosin (HE) ,periodic acid Schiff (PAS) ,Masson's Trichrome and immunohistochemical test for observation on morphology changes of airway remodeling. The cytokines of IFN γ and fL 4 in bronchoalveolar lavage fluid were measured by ELISA. The gene expression of IFN γ and IL 4 were measured by real time PCR. Results Compared with normal mice,the airway reactivity increased and the airway wall thickened in asthma group mice(P-<0. 05). Compared with mice with chronic asthma,the airway reactivity and remodeling significantly reduced in mice treated with HSP70/CD80 DNA vaccine(P<0. 05). The ratio of cy tokine IFN γ/IL 4 and the ratio of IFN γ/IL 4 gene expression were significantly higher than those of chronic asthma mice(P< 0. 05). Conclusion HSP70/CD80 DNA vaccine can delay the pathological changes of airway and reduce airway reactivity,thus re duce the development of airway of remodeling. The mechanism may be related to the promotion of IFN y production,enhancement Thl type immune response,and restoration of the Thl/Th2 balance.
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