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

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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14d雾化吸入布地奈德进行干预。于最后1次雾化后24h,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。 Objective To investigate the effect of thymus and activation regulated chemokine (TARC) in asthmatic rats and the effect of inhaled budesonide on TARC. Methods 30 SD rats were randomly divided into normal control group, asthma group and budesonide intervention group. Acute asthma model was induced by ovalbumin (OVA) sensitization in rats. The intervention group received inhaled budesonide for 14 days. At 24 h after the last nebulization, the tail vein was taken for blood and the bronchoalveolar lavage fluid (BALF) was taken from the bronchoalveolar lavage fluid and the right lung tissue samples were collected. Serum and BALF were assayed for cell count. Serum and BALF supernatants were assayed for levels of eosinophils (Eos), IL-4 and TARC using enzyme-linked immunosorbent assay (ELISA). The expression of TARC and IL-4 in lung tissue was detected by immunohistochemistry. Results 1) The levels of Eos, IL-4 and TARC in serum and BALF in asthma group were significantly higher than those in control group (P <0.05). The protein expressions of IL-4 and TARC in lung tissue were also higher than those in control group (P < 0.05). After the intervention of budesonide, the above indexes were all lower than the asthma group (P <0.05). There was no significant difference between the budesonide intervention group and the control group (P> 0.05). 2) The expression of TARC protein in lung tissue of asthmatic rats was positively correlated with IL-4 (r = 0.50, P <0.05). Conclusions The content of TARC in asthmatic rats is obviously increased. Budesonide inhalation can reduce the level of TARC. This suggests that TARC plays an important role in the pathogenesis of asthma. Down-regulation of TARC may be an important mechanism of hormonal treatment of asthma.
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