胸腺和活化调节趋化因子在哮喘大鼠中的作用及布地奈德干预的影响

目的 探讨胸腺和活化调节趋化因子(thymus and activation regulated chemokine, TARC)在哮喘大鼠中的作用及吸入布地奈德干预对TARC的影响。方法 30只SD大鼠采用随机区组设计分为正常对照组、哮喘组及布地奈德干预组。以卵清白蛋白(ovalbumin, OVA)致敏激发法制备大鼠哮喘急性模型, 干预组于14 d雾化吸入布地奈德进行干预。于最后1次雾化后24 h, 尾静脉取血, 支气管肺泡灌洗留取灌洗液(bronchoalveolar lavage fluid, BALF), 留取右肺组织标本。行血清和BALF中细胞计数, 应用酶联免疫吸附(ELISA)法测定血清和BALF中上清液中嗜酸粒细胞(Eos)、IL-4及TARC的水平。采用免疫组化法测定肺组织中TARC及IL-4蛋白的表达。结果 1) 哮喘组大鼠血清及BALF中的Eos、IL-4和TARC水平均高于对照组(P<0.05);肺组织中IL-4及TARC的蛋白表达也高于对照组(P<0.05);布地奈德干预后上述各项指标值均低于哮喘组(P<0.05), 布地奈德干预组的各项指标与对照组相比差异无统计学意义(P>0.05)。2)哮喘组大鼠肺组织中TARC的蛋白表达与IL-4呈正相关(r=0.50, P<0.05)。结论 哮喘大鼠中TARC含量明显增高, 吸入布地奈德可降低TARC的水平。提示TARC在哮喘的发病中起重要的作用, 下调TARC可能是激素治疗哮喘的一个重要机制。

Roles of thymus and activation regulated chemokine in asthmatic rats and interference of budesonide.

Objective To explore the role of thymus and activation regulated chemokine(TARC) in asthmatic rats and therapeutic effects of budesonide. Methods A total of 30 SD rats were randomly divided into normal group, asthmatic group, budesonide treated group, the rat model of asthma was established by the ovalbumin (OVA) provocation methods.The blood and bronchoalveolar lavage fluid (BALF) and lung tissue were collected 24 h after the last inhaling budesonide.The cells were counted, the concentrations of IL-4 and TARC in serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA).The IL-4 and TARC protein in lung tissue were detected by immnohistochemical method. Results 1)The counts of eosinophiles, the IL-4 and TARC levels in serum and BALF of asthmatic groups were significantly higher than those in normal group(P<0.05), and the expressions of IL-4 and TARC protein in lung tissue of asthmatic groups were obviously higher than those in normal groups (P<0.05);They were significantly increased when inhaling budesonide (P<0.05).There were no significances between the control groups and the budesonide treated groups (P>0.05).2)Significant association was found between expression of TARC and IL-4 in the lung tissue of asthma groups and they presented for positive correlations (r=0.50, P<0.05). Conclusions TARC levels were increased in asthmatic rats.Inhaling budesonide can decrease the levels of TARC, TARC plays an important role in the pathogenesis of asthma.Downregulation of TARC expression may be the important mechanism of budesonide to treat asthma.