雷公藤甲素对哮喘小鼠信号转导和转录激活因子6及eotaxin表达的影响

Effects of triptolide on the expression of STAT6 and eotaxin in asthmatic mice

目的研究雷公藤甲素对哮喘小鼠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,探讨其治疗哮喘的机制。方法建立小鼠卵蛋白哮喘模型,随机分为7组,分别为对照组、地塞米松治疗组及不同剂量雷公藤甲素治疗组,测定支气管肺泡灌洗液(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)及免疫组织化学法分别检测肺组织中STAT6、eotaxin mRNA及气道上皮STAT6、eotaxin蛋白表达水平。结果哮喘组STAT6、eotaxin mRNA及蛋白表达明显高于正常对照组(P<0.01),雷公藤甲素治疗组及地塞米松组明显低于哮喘组(P<0.01)。气道上皮STAT6的蛋白表达与BALF中白细胞数、Eos计数及气道上皮eotaxin蛋白表达呈正相关(r分别为0.528,0.612,0.682,P<0.01)。气道上皮eotaxin蛋白表达与白细胞总数、Eos计数呈正相关(r分别为0.79,0.88,P<0.01)。结论雷公藤甲素抑制哮喘气道炎症的机制可能与其抑制STAT6及eotaxin的表达活性有关。

Objective To study the effects of triptolide on the expression of STAT6 and eotaxin in asthmatic mouse model, and to explore the possible therapeutic mechanism of triptolide in asthma. Methods The asthmatic model was established by ovalbumin injection and inhalation. The mice were randomly divided into 7 groups and treated respectively with normal saline （as control）, dexamethasone or different dose of triptolide. The number of total leukocytes and eosinophils in branchoalveolar lavage fluid （BALF） was measured by light microscope. The mRNA of STAT6 and eotaxin in lung tissue and the protein expression in airway epithelium were detected by reverse transeription polymerase chain reactin （RT-PCR） and immunohistochemistry respectively. Results Eotaxin and STAT6 mRNA in lung tissue and the protein expression in airway epithelium of asthmatic group significantly increased compared with those of control group（P〈0.01）. The mRNA and protein expression of eotaxin and STAT6 in mice treated with different dose of triptolide and dexamethson were significantly lower than those in asthmatic group （P〈0.01 ）. STAT6 protein expression in airway epithelium was correlated with the number of total leukocytes and eosinphils in BALF and protein expression of eotaxin（ r =0.528,0.612 and 0.682, P〈0.01 ,respectively）. Eotaxin protein expression in airway epithelium was correlated with the number of total leukocytes and eosinphils in BALF （ r = 0.79 and 0.88, P〈0.01,respectively）. Conclusions The mechanism of triptolide inhibiting asthmatic airway inflammation may be related to its inhibiting activities of STAT6 and eotaxin.