磷脂酰肌醇3激酶促进支气管哮喘大鼠气道平滑肌细胞增殖

Phosphoinositide 3-kinases promotes proliferation of airway smooth muscle cells in asthmatic rats

目的探讨磷脂酰肌醇3激酶(PI3K)在支气管哮喘大鼠气道重构中的作用。方法将24只SD大鼠随机分为3组:正常对照组,哮喘4周组和6周组,每组8只。测定气道反应性并观察气道壁嗜酸性粒细胞的浸润情况;图像分析软件测定支气管壁厚度、支气管平滑肌厚度及支气管平滑肌细胞核数量;用免疫组织化学染色方法检测PI3K蛋白表达;逆转录聚合酶链反应(RT-PCR)检测PI3KmRNA表达。结果PI3K P85α主要在气道上皮细胞、气道平滑肌细胞表达。哮喘4周和6周组PI3K P85α蛋白及mRNA表达显著高于对照组(P<0.01),且6周组高于4周组(P<0.05,P<0.01);哮喘4周和6周组支气管壁厚度、支气管平滑肌厚度及平滑肌细胞核数量均较对照组明显增加(P<0.01),且6周组高于4周组(P<0.01);哮喘4周和6周组的气道反应性均高于对照组(P<0.01),且6周组高于4周组(P<0.05)。结论PI3K信号通路可能通过促进气道平滑肌细胞增殖参与哮喘气道高反应性及气道重构过程。

Objective To explore the effect of Phosphoinositide 3-Kinases （PI3 K） in airway remodeling in asthmatic rats. Methods Twenty-four rats were randomly divided into control group, asthmatic 4 weeks group and 6 weeks group （ n = 8 ）. The airway resistance and eosinophilic inflammation of airway wall were observed ; the airway wall thickness （WA/Pi）, the bronchial smooth muscle thickness （smooth muscle area/Pi） and the number of bronchial smooth muscle nucleus （N/Pi） were measured by image analysis system; the expression of PI3 K protein and mRNA were determined by immunohistochemical staining and reverse transcription-polymerase chain reaction （RT-PCR）. Results （1） The expression of PI3 K P85α was mainly located in the rat airway epithelial cells and airway smooth muscle cells. The expression of PI3 K P85 α protein and mRNA in two asthmatic groups was significantly higher than control group, respectively （ P 〈 0. 01 ）, and in asthmatic 6 weeks group was higher than asthmatic 4 weeks group, respectively （P 〈 0. 05, P 〈 0. 01 ）. （2） The airway wall thickness, bronchial smooth muscle thickness and the number of bronchial smooth muscle nucleus in two asthmatic groups were significantly higher than control group, respectively （ P 〈 0. 01 ） , and in asthmatic 6 weeks group were higher than asthmatic 4 weeks group, respectively （ P 〈 0. 01 ）. （ 3 ） The airway resistance in two asthmatic groups than control group, respectively（P 〈0. 01 ）, and in asthmatic 6 weeks group were higher group, respectively （P 〈 0. 05 ）. Conclusion The PI3 K signal pathway may be involved remodeling through promoting airway smooth muscle cells proliferation in asthma.