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中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (9): 961-968.doi: 10.12092/j.issn.1009-2501.2019.09.001

• 基础研究 •    下一篇

芍药苷通过PI3K/AKT/m-TOR信号途径抑制肥大细胞活化脱颗粒

虞姣姣,杨 洋,刘 莹,郭晓汐,徐天瑞,安 输   

  1. 昆明理工大学生命科学与技术学院,昆明 650500,云南
  • 收稿日期:2019-03-21 修回日期:2019-04-12 出版日期:2019-09-26 发布日期:2019-09-26
  • 通讯作者: 安输,男,博士,副教授,主要从事过敏反应发生机制及肿瘤和免疫方面的研究。 Tel:13769115084 E-mail:aslxj@mail.ustc.edu.cn
  • 作者简介:虞姣姣,女,在读博士生,主要从事过敏性疾病发生机制及肿瘤发展作用机理的研究。 Tel:15559888775 E-mail:yujjdo311@126.com
  • 基金资助:

    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)

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

YU Jiaojiao, YANG Yang, LIU Ying, GUO Xiaoxi, XU Tianrui, AN Shu   

  1. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
  • Received:2019-03-21 Revised:2019-04-12 Online:2019-09-26 Published:2019-09-26

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1,10,100 μg/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。

关键词: 芍药苷, 肥大细胞, 脱颗粒, 过敏反应

Abstract:

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 and β-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, 100 μg/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.

Key words: paeoniflorin, mast cell, degranulation, allergic reaction

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