布地奈德对哮喘气道重塑大鼠尾加压素-Ⅱ及mRNA表达的影响

Effect of Budesonide on the Expression of Urotensin-Ⅱ and Its mRNA in Asthma Airway Remodeling Rats

目的探讨布地奈德对哮喘气道重塑大鼠尾加压素-Ⅱ(U-Ⅱ)及其mRNA表达的影响。方法 24只清洁级雄性SD大鼠分为3组:对照组、哮喘组和布地奈德组。以卵清白蛋白(OVA)致敏激发法制备哮喘大鼠气道重塑模型,应用图像分析技术测定支气管壁厚度(Wat)和平滑肌厚度(Wam),酶联免疫吸附法(ELISA)测定血清和支气管肺泡灌洗液(BALF)中U-Ⅱ的浓度,免疫组化法和逆转录-聚合酶链反应(RT-PCR)法分别检测U-Ⅱ蛋白和U-ⅡmRNA在肺组织中的表达。结果①哮喘组Wat和Wam均显著高于对照组,布地奈德组Wat和Wam均显著低于哮喘组(均P<0.01);②哮喘组血清和BALF中U-Ⅱ的浓度均显著高于对照组,布地奈德组上述指标均显著低于哮喘组(均P<0.01);③免疫组化及RT-PCR结果显示,肺组织中U-Ⅱ蛋白及其mRNA的表达,哮喘组显著高于对照组,布地奈德组较哮喘组显著减弱(均P<0.01);④相关性分析显示,大鼠肺组织Wat与U-Ⅱ蛋白、U-ⅡmRNA表达呈正相关(均P<0.01),Wam与U-Ⅱ蛋白、U-ⅡmRNA表达呈正相关(均P<0.01)。结论布地奈德对哮喘气道重塑的拮抗作用,可能通过抑制U-Ⅱ的表达起作用。

OBJECTIVE To study the effects of budesonide （BUD） on the expression of urotensin- lI （UII） and its mRNA in asthma airway remodeling rats. METHODS Twenty-four Sprague-Dawley （SD） rats were randomly divided into three groups：the con- trol group, asthma group and BUD treated group. In the experiment, the models of asthma were established by sensitization and chal- lenge with ovalbumin（OVA）. The total brochial wall thickness （War） and the airway smooth tousle thickness （Warn） were measured by image analysis system. The levels of UII in BALF and serum were measured by enzyme linked immunosorbent assay （ELISA）. The protein and mRNA expression of UII were detected by immunohistoehemistry and reverse transcription polymerase chain reaction （ RT- PCR）, respectively. RESULTS Wat and Warn of of asthma group were significantly higher than those of the control group （ P 〈 0. 01, respectively）. Compared with asthma group, those were all markedly decreased in BUD group （ P 〈 O. 01, respectively）. The levels of UII in BALF and serum of asthma group were markedly higher than those in control group and BUD group （P 〈 0.01, re- spectively）. Immunohistoehemistry and RT-PCR showed that the protein and mRNA expression of UII in asthma group were significantly higher than those of control group （P 〈 0. 01, respectively）. While those of BUD group were significantly lower than those of asthma group（P 〈0.01, respectively）. There were a significantly positive correlation between Wat and the protein and mRNA expression of UII. At the same time, there were a significantly positive correlation between Warn and the protein and mRNA expression of UII. CONCLUSION The beneficial effect of glucocorticoid （BUD） on asthma airway remodeling may be at least in part due to their direct inhibitory effect on UII.