ERK信号转导通路在哮喘大鼠气道重塑中的作用  

作　　者：卢虹蓓[1] 李昌崇[1] 

机构地区：[1]温州医学院育英儿童医院,325027

出　　处：《浙江临床医学》2009年第5期452-455,共4页Zhejiang Clinical Medical Journal

基　　金：基金项目：国家自然科学基金资助项目（30271383）

摘　　要：目的研究在哮喘大鼠气道平滑肌细胞ASMC（airway smooth muscle cell）中ERK信号转导通路对哮喘气道重塑中的作用。方法原代培养ASMC，实验设未干预组（A组）、ERK阻断剂（U0126）组（B组）、PDGF组（C组）、PDGF＋ERK阻断剂组（D组）。B组又分为B1组、B2组、B3组、B4组，加入浓度分别为0．1μmol／L、1μmol／L、5μmol／L、10μmol／L的U0126；C组又分为C1组、C2组、C3组、C4组，加入浓度分别为1μg／L、10μg／L、25μg／L、50μg／L的PDGF—BB。免疫组化法测ERK。蛋白的表达（仅测A、B4、C4、D组），RT—PCR法测其mRNA表达。结果ASMC中ERK，蛋白表达B4组显著低于A组（P〈0．01），C4组显著高于A组（P〈0．01），D组与A组相比差异无统计学意义（P〉0．05）；B1组、B2组、B3组．B4组ERK，mRNA表达均显著低于A组（P〈0．01），U0126以浓度依赖性的方式抑制PDGF—BB诱导ASMC中ERK的活化；C1组、C2组、C3组、C4组ERK1 mRNA表达均显著高于A组（P〈0．01），ERK1 mRNA的表达与PDGF—BB存在明显的浓度依赖关系，D组则与A组相比差异无统计学意义（P〉0．05）。结论PDGF可剂量依赖地激活哮喘大鼠ASMC内的ERK通路，ERK通路参与了PDGF诱导的ASMC增殖的细胞内信号转导过程。Objective To explore the effect of ERK signal pathway on airway remodelling in ariway smooth muscle cells of asthmatic rats. Methods Smoth muscle cells of asthmatic rats were cultured and divided into four groups： control group（ groupA）, ERK blocking agent group （ U0126 ） group （ groupB ） , PDGF group （ groupC ） , PDGF ＋ ERK blocking agent group （ groupD ） ; and correspondingly group B was divided into four subgroups of groupB1, groupB2, groupB3, groupB4, interfered the ASMC with ERK specific inhibitor U0126 0. 1 μmol /L, 1 μmol /L, 5μmol /L respectively;group C was divided into four subgroups of group C1, groupC2, groupC3, groupC4, intervered the ASMC with recombinated rat PDGF- BB1μg /L, 10μg /L,25μg /L. 50μg /L respectively. The protein expressions of ERK1 were detected by immunohistochemistry technique, The mRNA expressions of ERK1 were detected by RT - PCR. Results The expression of ERK1 protein in ASMC of group B4 were significantly lower than that in group A（ P 〈 0. 01 ）, group C4 were significantly higher than group A（ P 〈 0. 01 ）, there were no significant difference between group D and group A（P 〉0. 05） ;the expressions of ERK1 protein in ASMC of group B1, B2. B3, B4 were significantly lower than group A（P 〈0. 01）, group C1 ,C2, C3, C4 were significantly higher than group A（P 〈 0.01 ）, there were no significant difference between group D and group A（P 〉 0.05 ）. Conclusions In ASMC, PDGF can dose - dependentandly induce the proliferation of ASMC and U0126 can block its effect. ERK signal pathway has very important effect on this process.

关 键 词：哮喘 大鼠 气道重塑 气道平滑肌细胞 

分 类 号：R692[医药卫生—泌尿科学] R733.7[医药卫生—外科学]