芍药苷通过PI3K/AKT/m-TOR信号途径抑制肥大细胞活化脱颗粒  

Paeoniflorin inhibits mast cell activation and degranulation through PI3K/AKT/m-TOR signaling pathway

作　　者：虞姣姣 杨洋[1] 刘莹[1] 郭晓汐 徐天瑞[1] 安输[1] YU Jiaojiao;YANG Yang;LIU Ying;GUO Xiaoxi;XU Tianrui;AN Shu(Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650500,Yunnan,China)

机构地区：[1]昆明理工大学生命科学与技术学院

出　　处：《中国临床药理学与治疗学》2019年第9期961-968,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金地区项目(81760264);云南省自然科学基金面上项目(2017FB045)

摘　　要：目的:研究芍药苷(paeoniflorin,Pae)对肥大细胞(P815)活化及脱颗粒的影响,并探索其作用机制。方法:CCK-8法评价Pae的细胞毒性,ELISA法及显色法测定Pae对P815释放组胺和β-氨基己糖苷酶(β-HEX)及IL-1β、IL-4、IL-8、IL-12的影响。实时荧光定量PCR(qRT-PCR)检测上述炎症因子及蛋白酶激活受体(PARs)在mRNA水平上的表达。Western blot测定磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)、哺乳动物雷帕霉素靶体蛋白(m-TOR)的磷酸化水平。结果:当芍药苷的浓度为1,10,100μg/mL时对P815无毒性,且能有效抑制组胺、β-HEX的释放及IL-1β、IL-4、IL-8、IL-12的分泌,并降低PARs的表达。Western blot显示,Pae能抑制PI3K、AKT、m-TOR的磷酸化。结论:Pae可能通过抑制PI3K/AKT/m-TOR信号通路实现对肥大细胞活化及脱颗粒的抑制作用。AIM:To study the effects of paeoniflorin on the activation and degranulation of mast cells(P815),and further to explore the mechanism.METHODS:The toxicity of paeoniflorin on P815 cells was evaluated by CCK-8 method.The effects of paeoniflorin on the release of histamine andβ-HEX and the secretion of inflammatory factors IL-1β,IL-4,IL-8 and IL-12 were determined by ELISA method and chromogenic method.The effects of paeoniflorin on the expression of inflammatory factors and PARs were detected by qRT-PCR.Western blot was used to study the phosphorylation levels of PI3K,AKT and m-TOR.RESULTS:Paeoniflorin had no cytotoxicity to P815 cells when the concentration was 1,10,100μg/mL,but effectively inhibited the release of histamine,β-HEX and IL-1β,IL-4,IL-8 and IL-12 after mast cells activation,and reduced the expression of PARs at the mRNA level.Additionally,paeoniflorin greatly reduced the phosphorylation levels of PI3K,AKT,m-TOR in mast cells treated with agonists.CONCLUSION:Paeoniflorin is an efficient inhibitor for mast cell activation and degranulation by blocking the PI3K/AKT/m-TOR signalling pathway.

关 键 词：芍药苷 肥大细胞 脱颗粒 过敏反应 

分 类 号：R965.2[医药卫生—药理学]