机构地区:[1]桂林医学院附属医院呼吸内科,广西桂林541001 [2]华中科技大学同济医学院同济医院呼吸内科,湖北武汉430030 [3]吉林大学环境与资源学院,吉林长春130012
出 处:《中国应用生理学杂志》2007年第3期359-364,I0005,共7页Chinese Journal of Applied Physiology
基 金:国家中医药管理局中医药留学回国人员科技活动择优资助课题;广西高校百名中青年学科带头人资助计划(桂教人[2005]64号);广西高校病理学科人才小高地创新团队计划(桂教人[2005]81号);广西科学基金项目(桂科自0679013)
摘 要:目的:探讨雷公藤内酯醇对哮喘气道重构及磷脂酰肌醇3激酶(PI3K)表达的影响。方法:将40只SD大鼠随机分为5组(n=8):A组(正常对照组);B组(哮喘4周组);C组(哮喘6周组);D组(给药4周组);E组(给药6周组)。测定气道反应性并观察气道壁嗜酸性粒细胞浸润;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;免疫组织化学染色、逆转录聚合酶链式反应(RT-PCR)检测PI3K蛋白及mRNA表达。结果:①B组、C组PI3Kp85α的蛋白及mRNA表达水平显著高于A组(P均<0.01),E组上述指标较B组、C组、D组均显著降低(P<0.01、P<0.01、P<0.05);②B组及C组支气管壁厚度、支气管壁平滑肌厚度、支气管壁平滑肌细胞核数量均较A组明显增加(P均<0.01),而E组上述指标较B组、C组、D组均显著降低(P均<0.01);③B组、C组的气道反应性均高于A组(P均<0.01),E组较B组、C组、D组均显著降低(P<0.01、P<0.01、P<0.05)。结论:气道平滑肌增生是气道重构的一个显著特征,PI3K可能在此起促进作用。雷公藤内酯醇可能通过下调PI3K的表达而减轻哮喘气道高反应性及抑制气道平滑肌增生,对哮喘气道重构有一定治疗作用。Aim:To explore the effect of Triptolide on airway remodeling and the expression of Phosphoinositide 3-Kinases in asthmatic rats.Methods:40 rats were randomly divided into 5 groups(n=8):①Control group;②Asthmatic 4 weeks group;③Asthmatic 6 weeks group;④Therapeutic 4 weeks group;⑤Therapeutic 6 weeks group.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 PI3K protein and mRNA were determined by immunohistochemical staining and reverse transcription-polymerase chain reaction(RT-PCR).Results:① The expression of PI3K p85α protein and mRNA in asthmatic 4 weeks group and asthmatic 6 weeks group were significantly hi-gher than control group,respectively(P〈0.01).The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group,asthmatic 6 weeks group and therapeutic 4 weeks group,respectively(P〈0.01,P〈0.01 P〈0.05).② The WA/Pi,the smooth muscle area/Pi and the N/Pi of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group,respectively(P〈0.01).The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group,asthmatic 6 weeks group and therapeutic 4 weeks group,respectively(P〈0.01).③The airway resistance of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than the control group,respectively(P〈0.01).The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group,asthmatic 6 weeks group and therapeutic 4 weeks group,respectively(P〈0.01,P〈0.01,P〈0.05).Conclusion:The proliferation of airway smooth muscle is a remarkable character of airway remodeling in asthma.The PI3K
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