平喘宁调节ERK信号通路干预哮喘气道重塑的机制

目的 通过观察平喘宁干预后哮喘模型大鼠ERK信号转导通路相关蛋白以及基质金属蛋白酶-9（matrix metalloproteinase-9, MMP-9）、金属蛋白酶组织抑制剂-1（tissue inhibitor of metalloproteinase-1, TIMP-1）的表达，探讨平喘宁调节寒性哮喘大鼠气道重塑的机制。方法 采用SPF级雄性SD大鼠复制寒性哮喘模型。将大鼠随机分成正常对照组，模型组，地塞米松组，桂龙咳喘宁组以及平喘宁高、中、低剂量组。连续给药4周后，光镜下观察肺组织病理形态学变化，采用免疫组织化学法检测肺组织中TIMP-1、MMP-9表达水平；采用Western blot法检测大鼠肺组织血小板源性生长因子（platelet derived growth factor, PDGF）、细胞外信号调节激酶-1（extracellular signal-regulated kinase 1，ERK1）、磷酸化细胞外信号调节激酶-1（phosphorylated ERK1, p-ERK1）的表达水平。结果 与正常对照组比较，模型组有明显炎性细胞浸润、气管上皮脱落增多、气管平滑肌增厚等气道重塑现象；与模型组比较，各治疗组炎性细胞浸润减少，气管上皮脱落减少，平滑肌增厚情况改善，气道重塑均得到适当缓解。与正常对照组比较，模型组MMP-9、TIMP-1的表达水平显著升高（P<0.05）；而与模型组比较，平喘宁各剂量组MMP-9、TIMP-1表达水平均显著下降（P<0.05），尤其是平喘宁高剂量组下降最为明显。与正常对照组比较，模型组PDGF以及ERK1、p-ERK1蛋白的表达水平显著升高（P<0.05）；而与模型组比较，药物治疗组PDGF以及ERK1、p-ERK1蛋白的表达水平均显著下降（P<0.05）。结论 平喘宁可通过调节ERK信号通路减轻哮喘大鼠气道炎性反应，延缓气道重塑。

Pingchuanning Exerts a Therapeutic Effect on Airway Remodeling in Asthma by Regulating the ERK Signaling Pathway

Objective To investigate the expression of the proteins associated with the ERK signaling pathway, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) after Pingchuanning intervention in a rat model of asthma and the mechanism of action of Pingchuanning in regulating airway remodeling in rats with cold-type asthma. Methods Male specific pathogen-free Sprague-Dawley rats were used to establish a model of cold-type asthma. The rats were randomly divided into normal group, model group, dexamethasone group, Guilong Kechuanning group, and high-, middle-, and low-dose Pingchuanning groups. After 4 weeks of consecutive administration,pathomorphological changes of the lung were observed under a light microscope; immunohistochemistry was used to measure the expression of TIMP-1 and MMP-9 in lung tissue; Western blot was used to measure the expression of platelet-derived growth factor (PDGF), extracellular signal-regulated kinase 1 (ERK1), and phosphorylated ERK1 (p-ERK1) in lung tissue. Results Compared with the normal group, the model group had marked inflammatory cell infiltration, increased airway epithelial shedding, and airway smooth muscle thickening; compared with the model group, each treatment group had reductions in inflammatory cell infiltration and airway epithelial shedding, an improvement in airway smooth muscle thickening, and remission of airway remodeling. Compared with the normal group, the model group had significant increases in the expression of MMP-9 and TIMP-1 (P<0.05); compared with the model group, the high-, middle-, and low-dose Pingchuanning groups had significant reductions in the expression of MMP-9 and TIMP-1 (P<0.05), and the high-dose Pingchuanning group had the greatest reductions. Compared with the normal group, the model group had significant increases in the expression of PDGF, ERK1, and p-ERK1 (P<0.05); compared with the model group, the treatment groups had significant reductions in the expression of PDGF, ERK1, and p-ERK1 (P<0.05). Conclusion Pingchuanning can reduce airway inflammation and delay airway remodeling in rats with asthma by regulating the ERK signaling pathway.