雷公藤多苷对哮喘大鼠气道转化生长因子-β_1 mRNA和Ⅲ型胶原表达的影响

Effects of Glucosida Tripterygii TOTA on expression of TGF-β_1-mRNA and type Ⅲ collagen in airways of asthmatic rats

目的探讨雷公藤多苷对支气管哮喘(简称哮喘)大鼠模型气道壁厚度及转化生长因子-β1 mRNA(TGF-β1 mRNA)和Ⅲ型胶原表达的影响及作用机制。方法健康雄性Wistar大鼠30只,随机数字表法分为对照组、哮喘组和雷公藤多苷组,每组10只。用卵白蛋白(OVA)致敏吸入激发制备哮喘模型。雷公藤多苷组给定量精制雷公藤多苷灌胃。采用逆转录-聚合酶链反应法(RT-PCR)测量肺组织的TGF-β1 mRNA和免疫组织化学方法测量气道壁Ⅲ型胶原的表达。组间比较采用单因素方差分析,组间差异比较用LSD方差分析法,采用Pearson相关分析;P<0.05为差异有统计学意义。结果①雷公藤多苷组TGF-β1 mRNA、Ⅲ型胶原表达分别为0.38±0.06、19.5±3.0,哮喘组分别为0.39±0.04、22.9±3.1,对照组分别为0.26±0.04、16.3±2.3,雷公藤多苷组与哮喘组比较差异有统计学意义(F值分别为18.42,14.1,P均<0.05);②Pearson相关分析表明TGF-β1 mRNA与Ⅲ型胶原的表达呈正相关(r=0.438,P<0.05);③气道壁厚度雷公藤多苷组为(15.9±2.3)μm,哮喘组为(20.1±2.9)μm,对照组为(11.6±2.4)μm,雷公藤多苷组与哮喘组比较差异有统计学意义(F值为27.12,P<0.05)。结论雷公藤多苷通过降低TGF-β1 mRNA的过度表达,抑制Ⅲ型胶原的沉积,减轻气道重塑的发生。

Objective To study the effects of Glucosida Tripterygii TOTA on transforming growth factor-beta 1 （TGF-β1） mRNA expression, type Ⅲ collagen and airway wall thickness of asthmatic rats and mechanism underlying these effects. Methods Thirty Wistar male rats were randomly divided into the control group, the asthmatic group or the Glucosida Tfipterygii TOTA treated group （n=10 each）. The rat model of asthma was established with ovalbumin inhalation. The Glucosida Tfipterygii TOTA group received metered dose of Glucosida Tripterygii TOTA by galvage. The expression of TGF-β1 mRNA in lung tissues was assessed with RT-PCR and the expression of airway type Ⅲ collagen with immunohistochemistry. SPSS 11.0 Software package was employed for all statistical analysis. The statistics were expressed as x±s. Group comparison was performed through one-way ANOVA while LSD was adopted to analyze inter-group difference. Pearson correlation analysis was used and P〈0.05 considered level of statistical significance. Results （1） The levels of expression of TGF-β1mRNA and type Ⅲ collagen were in 0.38±0.06 and 19.5±3.0 in the Glucosida Tripterygii TOTA treated group, 0.39±0.04 and 22.9±3.1 in asthmatic group, and 0.26±0.04 and 16.3± 2.3 in the control group, with significant difference between the Glucosida Tripterygii TOTA treated group and the asthmatic group （F=18.42 and 14.1, P〈0.05）. （2）Pearson correlation analysis showed that TGF-β1 mRNA was positively correlated with the expression of type Ⅲ collagen （r=0.438, P〈0.05）; （3）The thickness of airway wall was 15.9±2.3 μm in the Glucosida Tripterygii TOTA treated group, （20.1±2.9）μm in the asthmatic group and （11.6±2.4） μm in the control group, with significant difference between the Glucosida Tripterygii TOTA treated group and the asthmatic group （F=27.12, P〈0.05）. Conclusion Glucosida Tripterygii TOTA may delay the progression of airway remodeling by down-regulating the expressions of TGF-β1mRNA and suppressing the excess deposition of type Ⅲ collagen in extracellular matrix.