罗红霉素对哮喘平滑肌细胞增殖以及微囊蛋白-1及PI3K/Akt的影响  

Effect of roxithromycin on asthma smooth muscle cells proliferation,caveolin-1 and PI3K/Akt pathway

作　　者：徐慧[1] 戴元荣[1] 李凤琴[1] 付玉茹 夏梦玲[1] 葛翔挺 

机构地区：[1]温州医科大学附属第二医院呼吸科,浙江温州325027

出　　处：《中国药理学通报》2015年第3期407-411,共5页Chinese Pharmacological Bulletin

基　　金：浙江省自然科学基金资助项目(No Y2080466);温州市科技局项目(No Y20130351)

摘　　要：目的研究罗红霉素(RXM)能否通过上调微囊蛋白-1(caveolin-1)的表达来调控PI3K/Akt通路,从而抑制TGF-β1刺激引起的哮喘气道平滑肌细胞(ASMCs)增殖。方法 30只健康♂SD大鼠随机分为对照组和哮喘组,每组15只,以卵白蛋白(OVA)致敏和激发建立大鼠哮喘模型。将培养的ASMCs进行鉴定后,在哮喘组细胞中分别加入TGF-β1、PI3K/Akt通路抑制剂渥曼宁青霉素(wortmannin)、胆固醇剔除剂β-环糊精(β-CD)以及RXM进行干预,后三组在干预后再用TGF-β1刺激,故分6组:1TGF-β1组、2哮喘组、3正常组、4 wortmannin+TGF-β1组、5β-CD+TGF-β1组、6RXM+TGF-β1组,用CCK-8法检测哮喘大鼠ASMCs的增殖,Western blot检测ASMCs上caveolin-1、Akt、p-Akt的表达情况。结果 1TGF-β1组较正常组和哮喘组细胞增殖明显(P<0.01,P<0.05);RXM和wortmannin干预组较TGF-β1组细胞增殖减少(均P<0.01)。2与正常组比较,哮喘组、TGF-β1组、β-CD干预组气道平滑肌细胞caveolin-1的表达量明显减少(均P<0.05),TGF-β1组较哮喘组caveolin-1表达量明显减少(P<0.05);与此同时,哮喘组ASMCs较正常组p-Akt的表达量明显增加(P<0.05),TGF-β1组较哮喘组p-Akt表达量明显增加(P<0.05),wortmannin干预组较TGF-β1组p-Akt的表达量明显减少,β-CD干预组较TGF-β1组p-Akt表达量明显增加(P<0.05),RXM干预组较TGF-β1组p-Akt表达量明显减少(P<0.05)。结论罗红霉素可抑制TGF-β1刺激导致的哮喘大鼠ASMCs的增殖,并上调caveolin-1表达,抑制p-Akt活化。Aim To investigate the effect of roxithro-mycin（ RXM） on TGF-β1 induced airway smooth mus- cle cells （ ASMCs ） proliferation of asthmatic rats via caveolin-1 and PI 3 K/ Akt pathway . Methods Thirty male adult Sprague-Dawley rats were randomly divided into the normal group and the asthma group. Rat mod-els of chronic asthma were prepared and rats ASMCs were cultured in vitro. The asthmatic ASMCs with TGF-β1 , wortmannin （ inhibitor of PI3 K/Akt path-way）, β-cyclodextrin （cholesterol elimination agent） and RXM were interfered. The last three groups were stimulated with TGF-β1 . The cells were divided into：①TGF-β1 group,②asthma group,③normal group,④wortmannin ＋ TGF-β1 group, ⑤ β-CD ＋ TGF-β1 group,⑥RXM＋TGF-β1 group. Cells proliferation in each group was detected respectively with CCK8 meth-od, and the expressions of caveolin-1 and p-Akt pro-tein were detected with Western blot. Results The proliferation of ASMCs in TGF-β1 group increased sig-nificantly compared with that in normal group and asth-ma group（P〈0. 01,P 〈0. 05）. While the ASMCs in the TGF-β1 ＋ wortmannin group, RXM ＋ TGF-β1 group decreased significantly compared with those in TGF-β1 group（P〈0. 01）. The expression of caveolin-1 in ASMCs of asthmatic group,TGF-β1 group, β-CD＋TGF-β1 group decreased significantly compared with that in the normal group（P〈0. 05）, and that in TGF-β1 group was less than in asthma group （ P 〈0. 05 ） . The expression of p-Akt in ASMCs of asthma group in-creased significantly compared with that in normal group（P〈0. 05）, and that in TGF-β1 group increased more than that in asthma group（P〈0. 05）,while that in β-CD＋TGF-β1 group increased more than that in TGF-β1 group. The expression of p-Akt in RXM ＋TGF-β1 group was less than that in TGF-β1 group. Conclusion RXM may supress TGF-β1-induced ASMCs proliferation in asthmatic rats, increase the ex-pression of caveolin-1,and depress the activation of p-Akt.

关 键 词：罗红霉素 微囊蛋白 磷脂酰肌醇3激酶 气道平滑肌细胞 哮喘 气道重塑 

分 类 号：R332[医药卫生—人体生理学] R322.74[医药卫生—基础医学]