摘要
目的探讨地塞米松对哮喘小鼠胸腺活化调节趋化因子(TARC)及其mRNA表达的影响。方法30只清洁级雄性BALB/C小鼠分为3组:正常对照组、哮喘组和地塞米松组。以卵清白蛋白(OVA)致敏激发法制备小鼠哮喘模型,末次激发24h后留取支气管肺泡灌洗液(BALF)及肺组织。BALF行嗜酸性粒细胞(EOS)计数及分类;采用酶联免疫吸附法(ELISA)测BALF中TARC和IL-4水平;免疫组化法和逆转录-聚合酶链反应(RT-PCR)法分别检测TARC蛋白和TARC mRNA在肺组织中的表达。结果①哮喘组BALF中细胞总数,EOS绝对数和EOS占细胞总数的百分数(EOS%)均显著高于正常对照组,地塞米松组上述指标均显著低于哮喘组(均P<0.01);②哮喘组BALF中TARC,IL-4浓度均显著高于对照组,地塞米松干预后BALF中TARC,IL-4浓度均显著低于哮喘组(均P<0.01)。③免疫组化及RT-PCR结果显示,肺组织中TARC蛋白及其mR-NA的表达,哮喘组显著高于对照组,地塞米松组较哮喘组显著减弱(均P<0.01),免疫组化显示,TARC蛋白主要表达于支气管上皮细胞。④相关性分析显示,小鼠BALF中TARC浓度与EOS绝对值、IL-4浓度均呈显著正相关(均P<0.01)。结论糖皮质激素(地塞米松)可抑制TARC在哮喘小鼠气道上皮中的表达,可能是其治疗哮喘气道炎症的部分作用机制。
Abstract
OBJECTIVE To study the effects of dexamethasone on the expression of thymus and activation-regulated chemokine (TARC) and its mRNA in asthmatic mice.METHODS Thirty male Balb/ C mice were randomly divided into three groups : the control group, asthma group and dexamethasone (DXM ) treated group. In the experiment , the mice models of asthma were established by sensitization and challenge with ovalbumin (OVA). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected from mice 24 h after the last challenge . The total cell numbers, Eosinophils (EOS) numbers and the cell differentials of BALF cells were counted. The levels of TARC and IL-4 in BALF were measured by enzyme-linked immunosorbent assay (ELISA). The expression of TARC protein and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), respectively. RESULTS The total cell numbers in BALF,the absolute numbers of EOS, the ratios of EOS to the total cell numbers(EOS%) of asthma group were all significantly higher than those of the control group(P<0.01, respectively).Compared with asthma group, those were all markedly decreased in DXM group(P<0.01, respectively). The levels of TARC and IL-4 in BALF of asthma group were markedly higher than those in control group and DXM group(P<0.01, respectively). Immunohistochemistry and RT-PCR showed that the protein and mRNA expression of TARC in asthma group were significantly higher than that of control group (P<0.01, respectively).While that of DXM group were significantly lower than that of asthma group ( P<0. 01,respectively). Immunohistochemistry also showed that the predominant cells in lung tissues that expressed TARC were epithelial cells. Strong positive correlations were found between TARC and absolute numbers of EOS and IL-4 in BALF.CONCLUSION The beneficial effect of glucocorticoid (dexamethasone) on airway inflammation may be at least in part due to their direct inhibitory effect on TARC generation by the bronchial epithelium.
关键词
哮喘 /
胸腺活化调节趋化因子 /
地塞米松 /
小鼠
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Key words
asthma /
thymus and activation-regulated chemokine /
dexamethasone /
mice
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郑吉善;苏苗赏;李昌崇;叶乐平;董琳;罗运春;陈小芳;李孟荣;张正霞.
地塞米松对变应性哮喘小鼠胸腺活化调节趋化因子及mRNA表达的影响[J]. 中国药学杂志, 2007, 42(22): 1709-1713
ZHENG Ji-shn;SU Mio-shng;LI Chng-chong;YE Le-ping;DONG Lin;LUO Yun-chun;CHEN Xio-fng;LI Meng-rong;ZHNG Zheng-xi.
Effects of Dexamethasone on the Expression of Thymus and Activation- Regulated Chemokine and Its mRNA in Murine Model with Allergic Asthma [J]. Chinese Pharmaceutical Journal, 2007, 42(22): 1709-1713
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脚注
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基金
浙江省自然科学基金资助项目(Y205426)
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