中文摘要：

目的：研究血小板源性生长因子（PDGF）对哮喘大鼠气道平滑肌细胞（ASMC）中ERK信号通路的调控作用。方法建立哮喘大鼠模型，原代分离培养ASMC，设未干预组（A组）、ERK阻断剂组（B组）、PDGF组（C组）和PDGF＋ERK阻断剂组（D组）。A组不加干预；B组又分为B1、B2、B3、B4组，分别加入浓度为0.1、1、5、10μmol/L的ERK阻断剂U0126；C组又分为C1、C2、C3、C4组，分别加入浓度为1、10、25、50μg/L的PDGF同二聚体PDGF- BB；D组加入10μmol/L的U0126和50μg/L的PDGF- BB。以RT- PCR法检测各组ERK1和TGF-β1的mRNA表达，免疫组化法检测A、B4、C4和D组中以上蛋白的表达。结果 RT- PCR提示B1、B2、B3、B4组ERK1 mRNA表达均显著低于A组（均P＜0.01），U0126以浓度依赖的方式抑制PDGF诱导的ASMC中ERK的活化，C1、C2、C3、C4组ERK1 mRNA表达均显著高于A组（均P＜0.01），ERK1 mRNA的表达与PDGF- BB存在明显的浓度依赖关系，D组与A组比较无统计学差异（P＞0.05）。免疫组化提示B4组ASMC中ERK1蛋白表达显著低于A组，C4组显著高于A组（均P＜0.01），D组与A组相比无统计学差异（P＞0.05）；B4组TGF-β1蛋白表达显著低于A组，C4组显著高于A组，同时C4组显著高于B4组（均P＜0.01），D组与A组相比无统计学差异（P＞0.05）。结论 PDGF可剂量依赖性激活哮喘大鼠ASMC内的ERK通路，同时伴随TGF-β1信号通路的活化。ERK通路参与了ASMC增殖的细胞内信号转导过程，PDGF可能经ERK环节促进TGF-β1通路活化。

英文摘要：

Objective To investigate the effect of platelet- derived growth factor （PDGF）on proliferation of airway smooth muscle cells （ASMC） in asthmatic rats and its relation to external signal regulated kinase （ERK） signal pathway. Methods Asth-ma model was established in Sprague- Dawley rats. ASMCs separated from asthmatic rats were divided into four groups：group A without any intervention served as control, group B was treated with ERK blocking agent U0126 0.1μmol/L（B1）, 1μmol/L （B2）, 5μmol/L （B3） or 10μmol/L （B4）, group C was treated with recombinant rat PDGF- BB 1μg/L （C1）, 10μg/L （C2）, 25μg/L （C3） or 50μg/L （C4）, group D was treated with 10μmol/L U0126 and 50μg/L PDGF. The mRNA expressions of ERK1 and TGF- β1 in ASMCs of asthmatic rats were detected by RT- PCR. The protein expressions of ERK1 and TGF- β1 were detected by immuno-histochemistry （group A, B4, C4 and D only）. Results Compared to group A, the expressions of ERK1 mRNA in ASMCs of groups B1, B2, B3 and B4 were significantly decreased（P〈0.01） in a concentration- dependent manner;while the expressions of ERK1 mRNA in groups C1, C2, C3 and C4 were significantly increased （P〈0.01） in a concentration- dependent manner. There was no significant difference in expressions of ERK1 mRNA between group D and group A （P〉0.05）. Immunohistochemistry showed that the expression of P- ERK1 in ASMCs of group B4 was significantly lower and that of group C4 was higher than that in group A （both P〈0.01）;while there was no significant difference between group D and group A （P〉0.05）. Conclusion PDGF can induce the proliferation of airway smooth muscle cells of asthmatic rats, in which the activation of ERK signal pathway is in-volved.