PACAP38对支气管哮喘小鼠肺组织TSLP蛋白表达的影响及机制研究

Effect and mechanism of PACAP38 on expression of TSLP in lung tissues of asthmatic mice

目的应用PAC1R（PACAP38的特异性受体）阻滞剂PACAP6—38，探讨PACAP38对支气管哮喘（简称哮喘）小鼠炎性介质胸腺基质淋巴细胞生成素（TSLP）的影响及其可能机制。方法建立小鼠卵白蛋白致敏和激发的哮喘模型。60只SPF级雄性BALB／c小鼠，随机分为6组，每组10只：溶剂对照组（A组）、哮喘模型组（B组）、地塞米松组（C组）、PACAP38组（D组）、PACAP6-38组（E组）、PACAP38＋PACAP6—38组（F组）。免疫组织化学、逆转录多聚酶联反应检测NF-κBp65、TSLP的表达情况。结果肺组织中TSLP、NF-κBp65蛋白表达B组显著高于A组（P〈0．01）；C组、D组较B组下降（P〈0．01）；E组、F组与B组比较差异无统计学意义（P〉0．05）。结论PACAP38可通过与PAC1R结合，通过NF—κB信号转导通路，抑制炎症因子TSLPmRNA及蛋白的表达。

Objective To explore the effect of PACAP38 in regulation of thymic stromal lymphopoietin （TSLP）expression in lung tissue, applied the PAC1 R（the specific receptor of PACAP38） blockers PACAP6-38, discussed its probable mechanism in asthmatic model. Methods Established the mouse asthma model by sensitization with Ovalbumin Al（OH）3 ,sixty male BALB/c mice, were randomly divided into six groups,including solvent controls group （group A, n = 10）, asthma group （group B, n =10） ,dexamethasone group （group C, n = 10） ,PACAP38 group （group D, n = 10） ,PACAP6-38 group （group E, n = 10） and PACAP38＋PACAP6-38 group, （group F, n =10）. The expression of TSLP, NF-κBp65 were detected by reverse transcriptase polymerase chain reaction, immunohistochemistry. Results lmmunohistochemical staining manifested that TSLP, NF-κBp65 protein expressed in lung in group B were markedly higher than that of group A（ P 〈0.01） ,group C,group D were lower than group B （P 〈0.01）, their was no apparent difference among group E, group F and group B （P 〉 0.05）. Conclusions PACAP38 can be combined with PAC1 R, via NF-κB signal transduction pathway,inhibited the expression of inflammatory cytokine TSLP mRNA and protein.