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 signal pathway may be involved in the process.Triptolide may reduce AHR and decrease the proliferation of ASMCs by inhibiting the expression of PI3K.It may have potential therapeutic effects in the asthmatic airway remodeling.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
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)