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目的研究细胞外信号调节激酶(ERK)和转化生长因子β1(TGF-β1)在哮喘气道重塑中的作用,探讨糖皮质激素对 ERK、TGF-β1及哮喘气道重塑的调控。方法建立慢性哮喘动物模型,将30只 SD 大鼠随机分对照组、哮喘组、地塞米松干预组(DM 组)。免疫组化测定肺组织中磷酸化的 ERK(P-ERK),ELISA 测定血清中 TGF-β1含量。体外培养大鼠气道上皮细胞,以 BB 型血小板源性生长因子(PDGF-BB)、U0126、布地奈德(BUD)作为工具药干预细胞,Western 印迹检测细胞 ERK磷酸化水平,ELISA 法检测细胞上清液 TGF-β1含量。结果哮喘组 P-ERK 平均吸光度和 TGF-β1含量[分别为(31.1±2.2)和(28.1±7.4)μg/L]均较对照组[(12.8±2.4)和(13.6±2.7)μg/L]高(P<0.01),DM 组[分别为(18.7±3.1)和(15.0±3.2)μg/L]较哮喘组低(P 均<0.01)。ERK 的磷酸化与 PDGF-BB 存在浓度依赖关系,50μg/L 时 ERK 磷酸化水平最高,高于对照组(P<0.01);U0126和 BUD 均可抑制 ERK 的磷酸化;各处理组细胞上清 TGF-β1差异无统计学意义。结论 ERK磷酸化、TGF-β1在支气管哮喘气道重塑中起重要作用;PDGF-BB 不能通过 ERK 磷酸化诱导正常大鼠气管上皮细胞产生释放 TGF-β1;糖皮质激素能抑制 ERK 磷酸化。
Objective To investigate the role of extracellular signal-regulated kinase (ERK) and transforming growth factor-β1 (TGF-β1) in the airway remodeling of asthma and to investigate the regulation of glucocorticoid on ERK, TGF-β1 and airway remodeling in asthma. Methods The animal model of chronic asthma was established. Thirty SD rats were randomly divided into control group, asthma group and dexamethasone intervention group (DM group). The phosphorylated ERK (P-ERK) in lung tissue was detected by immunohistochemistry and the content of TGF-β1 in serum by ELISA. The rat airway epithelial cells were cultured in vitro and the cells were treated with PDGF-BB BB, U0126 and budesonide (BUD) as tools, the phosphorylation of ERK was detected by Western blot, Supernatant TGF-β1 content. Results Compared with the control group [(12.8 ± 2.4) and (13.6 ± 2.7) μg / L, the mean absorbance of P-ERK and the content of TGF-β1 in the asthmatic group were (31.1 ± 2.2) and (28.1 ± 7.4) μg / ] (P <0.01), DM group [(18.7 ± 3.1) and (15.0 ± 3.2) μg / L] were lower than those in asthma group (all P <0.01). ERK phosphorylation and PDGF-BB concentration-dependent relationship, 50μg / L ERK phosphorylation level was higher than the control group (P <0.01); U0126 and BUD can inhibit ERK phosphorylation; the cell supernatant of each treatment group TGF-β1 difference was not statistically significant. Conclusion ERK phosphorylation and TGF-β1 play an important role in the airway remodeling of bronchial asthma. PDGF-BB can not induce the release of TGF-β1 from normal rat tracheal epithelial cells through phosphorylation of ERK. Glucocorticoid can inhibit ERK phosphorylation.