砒石对哮喘小鼠信号转导和转录激活因子6及嗜酸粒细胞趋化因子mRNA表达的影响

Effects of arsenolite on expressions of signal transducer and activator of transcription 6 and eotaxin(mRNA) in asthmatic mice

目的观察砒石对哮喘小鼠肺组织中信号转导和转录激活因子6(STAT6)、嗜酸粒细胞趋化因子(eotaxin)表达的影响,探讨砒石防治哮喘的作用机制。方法56只昆明种雌性小鼠随机分为7组(n=8):正常对照组,哮喘模型组,地塞米松组,砒石0.575 mg/kg(AS0.575)组,砒石1.15 mg/kg(AS1.15)组,砒石2.3 mg/kg(AS2.3)组,砒石4.6 mg/kg(AS4.6)组;建立卵蛋白(OVA)哮喘模型,测定各组肺功能,检测支气管肺泡灌洗液(BALF)中白细胞总数及嗜酸粒细胞(EOS)计数;逆转录-聚合酶链反应(RT-PCR)法检测肺组织中STAT6、eotaxin mRNA表达水平。结果小鼠致敏3周及激发3 d后,肺功能测定表现为呼气相时间明显延长,呼气相最大压力明显增大,与正常对照组比较有显著性差异(P<0.01);哮喘组BALF中白细胞总数及EOS计数,肺组织STAT6、eotaxin mRNA表达水平较正常对照组明显升高(P<0.01);经地塞米松和不同剂量砒石处理后哮喘小鼠BALF中白细胞总数、EOS计数、肺组织中STAT6和eotaxin mRNA的表达水平较哮喘组下降(P<0.01),砒石对STAT6和eotaxin mRNA表达的抑制作用呈剂量效应关系。结论STAT6和eotaxin在哮喘气道炎症的发生、发展中起重要作用;砒石可显著抑制哮喘小鼠肺组织中STAT6和eotaxin mRNA表达,降低哮喘小鼠BALF中白细胞总数及EOS计数,减轻哮喘气道黏膜炎症。

Obejective To investigate the effects of arsenolite on the expressions of signal transducer and activator of transcription 6（STAT6） and eotaxin mRNA in asthmatic mice and the possible mechanism of arsenolite in asthma therapy. Methods 56 healthy Kunming female mice weighted （20± 3） g were randomly divided into 7 groups （ n = 8）, ie. normal group （group N）, asthmatic group （group A）, dexamethasone group （group D）, arsenolite 0.575 mg/kg group （group AS0.575）, arsenolite 1.15 mg/kg group （group AS1.15）, arsenolite 2.3 mg/kg group （group AS2.3）, and arsenolite 4.6 mg/kg group （group AS4.6） .The asthmatic model was established by ovalbumin sensitization and challenge. The numbers of total leukocytes and eosinophils in bronchoalveolar lavage fluid （BALF） were counted under a light microscope. RT-PCR was employed to detect mRNA for STAT6 and eotaxin in the lung tissue. Results After sensitization of 3 weeks and challenge of 3 days, the animals expressed prolonged expiratory time and elevated expiratory pressure in pulmonary function testing compared to those in group N. The numbers of total leukocytes and eosinophils in BALF, and the levels of STAT6 and eotaxin mRNA expression in group A were significantly increased compared with group N （ P 〈 0.01） .After treated with different doses of arsenolite and dexamethasone, the numbers of total leukeeytes and eosinophils in BALF were decreased and the expression of STAT6 and eotaxin mRNA were suppressed significantly （P 〈 0.01 ）. Moreover, the mRNA expressions were suppressed in a dose dependent manner. Conclusions STAT6 and eotaxin may play a crucial role in the pathogenesis of allergen-induced airway inflammation in asthma. Arsenolite can significantly inhibit the expressions of STAT6 and eotaxin mRNA and decrease leukocytes and eosinophil infiltration.Therefore, arsenolite may be of potential value in the prevention and treatment of asthma.