CAJ | 학술논문

目的评价虫草素及虫草素与糖皮质激素联合应用对慢性哮喘模型小鼠气道平滑肌收缩的调节作用及可能机制.方法将32只C57/BL6小鼠随机分成对照组和慢性哮喘模型组,利用肌动描记仪比较p38蛋白激酶抑制剂SB239063(10-6M)、虫草素(10-6M)以及糖皮质激素地塞米松(10-6M)单独或联合孵育前、后由乙酰胆碱(acetylcholine,Ach)诱导的支气管收缩反应,同时应用蛋白印迹检测支气管组织中p38蛋白激酶和热休克蛋白27(heat shock proteins 27,HSP27)的磷酸化状态.结果模型组小鼠的支气管收缩较对照组加重,有统计学意义.对照组和模型组p38蛋白激酶抑制剂SB239063孵育1h后对Ach介导的收缩反应较空白对照组下降(P＜0.05),地塞米松单独和地塞米松联合虫草素在模型组小鼠Ach诱导支气管平滑肌收缩力的作用均较对照组降低(P＜0.05)；地塞米松单独和地塞米松联合虫草素孵育后,对照组和模型组小鼠支气管组织p38蛋白激酶和HSP27磷酸化水平较Ach单纯作用组降低,而且在模型组,使用虫草素干预后p38蛋白激酶和HSP27磷酸化水平较Ach单纯作用组下降(P值均＜0.05).结论 Ach诱导的离体支气管收缩反应具有良好的可重复性,卵清白蛋白吸入可导致Ach诱导的支气管收缩反应加重,糖皮质激素联合虫草素治疗较糖皮质激素单独治疗更有效抑制Ach诱导的气道平滑肌收缩,此种潜在的协同作用可能通过更大程度地抑制p38蛋白激酶信号通路为机制.
목적 평개충초소급충초소여당피질격소연합응용대만성효천모형소서기도평활기수축적조절작용급가능궤제.방법 장32지C57/BL6소서수궤분성대조조화만성효천모형조,이용기동묘기의비교p38단백격매억제제SB239063(10-6M)、충초소(10-6M)이급당피질격소지새미송(10-6M)단독혹연합부육전、후유을선담감(acetylcholine,Ach)유도적지기관수축반응,동시응용단백인적검측지기관조직중p38단백격매화열휴극단백27(heat shock proteins 27,HSP27)적린산화상태.결과 모형조소서적지기관수축교대조조가중,유통계학의의.대조조화모형조p38단백격매억제제SB239063부육1h후대Ach개도적수축반응교공백대조조하강(P＜0.05),지새미송단독화지새미송연합충초소재모형조소서Ach유도지기관평활기수축력적작용균교대조조강저(P＜0.05)；지새미송단독화지새미송연합충초소부육후,대조조화모형조소서지기관조직p38단백격매화HSP27린산화수평교Ach단순작용조강저,이차재모형조,사용충초소간예후p38단백격매화HSP27린산화수평교Ach단순작용조하강(P치균＜0.05).결론 Ach유도적리체지기관수축반응구유량호적가중복성,란청백단백흡입가도치Ach유도적지기관수축반응가중,당피질격소연합충초소치료교당피질격소단독치료경유효억제Ach유도적기도평활기수축,차충잠재적협동작용가능통과경대정도지억제p38단백격매신호통로위궤제.
Objective To investigate the role of cordycepin on airway smooth muscle contraction and the potential role of p38 mitogen-activated protein kinases (p38MAPK) in airway smooth muscle contractile response.Methods C57/BL6 mice were divided into air exposure and ovalbumin (OVA)exposure group,the bronchi were isolated from them and incubated with vehicle,p38MAPK inhibitor SB239063(10-6 M),Dexamethasone (Dex) and/or codycepin (10-6 M).Acetylcholine (Ach) induced bronchial contractile responses were measured hefore and after incubation using myograph.Western blot analysis was used to measure the phosphorylation of p38MAPK and heat shock proteins 27(HSP27).Results Bronchial contractile responses to Ach were significantly enhanced in OVA exposed mice than in air exposed mice.Either 10-6 M SB239063 or 10-6 M Dex and/or 10-6 M cordycepin could equally inhibit Ach induced bronchial contraction Emax in both groups (P ＜0.05),while cordycepin alone failed to do so.Dex and/or cordycepin could inhibit the pbosphorylation of p38MAPK than Ach stimulated group significantly in air/OVA exposure mice,while the remarkably inhibition was shown in OVA exposure mice when pretreated with cordycepin,Dex and/or cordycepin could inhibit the phosphorylation of HSP27 than Ach stimulated group significantly in air/OVA exposure mice.Conclusions Ach induced exvivo bronchial contractility was highly reproducible,while OVA exposure could enhance the airway smooth muscle contraction.p38MAPK was involved in Ach induced airway smooth muscle contractility.Dex and Cordycepin could more effectively inhibit airway smooth muscle contraction than Dex alone,those effects may be p38MAPK/HSP27 dependent.