ERK1/2信号通路在大鼠气道黏液高分泌中的作用研究

Effect of ERK1/2 pathway on airway mucus hypersecretion in rats

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。

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. 25ms/ks, 0. 5ms/ks and 1 ms/ks 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.