【摘要】 目的:探讨细胞外信号通路1/2(ERK1/2)在气道黏液高分泌过程中的作用。方法:通过大鼠气道内注入脂多糖(LPS)并烟熏建立气道黏液高分泌模型。分别给予ERK1/2特异性阻断剂-U01260.25mg/kg、0.5mg/kg和1mg/kg腹腔注射14d。提取肺组织,采用免疫组化、RT-PCR等方法检测Muc5ac、ERK1/2及磷酸化ERK1/2(p-ERK1/2)等的表达水平。结果:LPS及烟熏刺激可以使大鼠气道上皮Muc5ac mRNA和蛋白的表达增多,并引起p-ERK1/2与ERK1/2比值明显增高。U0126可以抑制由LPS导致的气道Muc5ac高表达和p-ERK1/2与ERK1/2比值增高。p-ERK1/2与ERK1/2的比值与Muc5ac mRNA和蛋白的表达呈正相关关系。结论:U0126可抑制LPS及烟熏所致的气道黏液高分泌状态,其机制可能是ERK1/2信号通路参与了气道黏液高分泌的调控,U0126通过特异性阻断ERK1/2从而导致黏液高分泌的下调。更多还原

【Abstract】 Objective:To examine the effect of ERK1/2 (extracellular signal-regulated kinases 1/2,ERK1/2) pathway on airway mucus hypersecretion stimulated by lipopolysaccharide (LPS) and smoking in rats.Methods: Rat airway mucus hypersecretion was induced by intratracheal instillation of LPS and smoking.Rats treated with LPS and smoking were administered with U0126 0.25mg/kg,0.5mg/kg and 1 mg/kg separately by intraperitoneal injection for 14 days.The mRNA and protein expression of Muc5ac, ERK1/2 and p-ERK1/2(phosphorylated extracellular signal-regulated kinases1/2, p-ERK1/2) were detected by RT-PCR and immunohistochemistry.Results: LPS and smoking significantly induced the expression of Muc5ac mRNA and protein in bronchial epithelia, and increased the ratio of p-ERK1/2 and ERK1/2. U0126 significantly suppressed the expression of Muc5ac mRNA and protein induced by LPS and smoking. Moreover, there was significant positive correlation between the ratio of p-ERK1/2 and ERK1/2 and the expression of Muc5ac mRNA and protein. Conclusion: U0126 inhibits pulmonary inflammatory response and airway mucus hypersecretion induced by LPS and smoking,which might be ascribed to the inhibition of ERK1/2.更多还原