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中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (3): 290-293.

• 研究原著 • 上一篇    下一篇

青蒿素对CpG DNA 攻击小鼠保护作用的实验研究

王俊, 周红   

  1. 第三军医大学药理教研室, 重庆400038
  • 收稿日期:2004-12-29 修回日期:2005-02-28 出版日期:2005-03-26 发布日期:2020-11-18
  • 通讯作者: 周红, 女, 博士后, 教授, 博士生导师, 主要研究方向:感染、炎症的发病机制及其防治措施的研究。Tel:023-68752266 E-mail:zhouh64@mail.tmmu.com.cn
  • 作者简介:王俊, 男, 硕士研究生。Tel:023-68752265 E-mail:wjun2000@yahoo.com.cn
  • 基金资助:
    国家重点基础研究发展规划973 项目资助课题(NoG1999054203)

Protective effects of artemisinin challenged with CpG DNA in mice

WANG Jun, ZHOU Hong   

  1. Department of Pharmacology, College of Medicine, the Third Military Medical University, Chongqing 400038, China
  • Received:2004-12-29 Revised:2005-02-28 Online:2005-03-26 Published:2020-11-18

摘要: 目的:观察青蒿素对CpG DNA 攻击小鼠的保护作用及对CpG DNA 诱导小鼠单核 巨噬细胞RAW264.7 释放促炎细胞因子的影响。方法:清洁级昆明小鼠60 只, 随机分为CpG DNA、青蒿素(200mg°kg-1)、CpG DNA+青蒿素(50、100、200 mg°kg-1)及生理盐水对照组, 每组动物10 只。CpG DNA 及CpG DNA+青蒿素组小鼠提前1 h 腹腔注射D-氨基半乳糖溶液(600 mg°kg-1)进行敏化。CpG DNA 组尾静脉给予4 mg°kg-1的CpG DNA 敏化;青蒿素组,灌胃给予200 mg°kg-1的青蒿素;CpG DNA+青蒿素组在给予不同剂量的青蒿素后, 立即给予40mg°kg-1的CpG DNA 敏化;生理盐水对照组仅给予相同量的生理盐水。体外培养小鼠巨噬细胞RAW264.7, 加入不同浓度的青蒿素, 观察其对CpG DNA刺激细胞分泌TNF-α及IL-6 的拮抗作用及其量效、时效关系。结果:青蒿素可降低CpG DNA 引起的小鼠死亡, 死亡率由80% 降至10% (P<0.01)。青蒿素在20 g°ml-1 时显著抑制CpG DNA 诱导RAW264.7 释放TNF-α和IL-6(P<0.01)。提前给予青蒿素, 其拮抗CpG DNA 诱导细胞因子释放的作用非常显著(P<0.01), 但青蒿素在刺激物CpG DNA 给予后再加入, 也能观察到显著拮抗作用(P<0.05)。结论:青蒿素对CpG DNA 攻击小鼠具有显著保护作用, 该保护作用可能与其明显抑制CpG DNA 诱导的促炎细胞因子释放有关。

关键词: 青蒿素, SIRS, CpGDNA, 促炎细胞因子, 内毒素

Abstract: AIM: To investigate the protective effects of artemisinin on mice and its inhibition effects on the release of pro-inflammatory cytokines challenged with CpG DNA.METHODS: A total of 60 mice of Kunming species were randomly divided into six groups.Animals received an intraperitoneal injection of D-galactosamine (D-Gal, 600 mg°kg-1)1 hour prior to intravenous injection of CpG DNA.CpG DNA group received CpG DNA at 4 mg°kg-1 via caudal vein, artemisinin group were orally administered artemisinin at 200 mg°kg-1, CpG DNA plus artemisinin group first received artemisinin at 50, 100, and 200 mg°kg-1, respectively, then received CpG DNA at 4 mg°kg-1, and the control group received the saline only.The mortality was observed within seven days after injection.RAW 264.7 cell lines were cultivated in vitro and stimulated by CpG DNA to release TNF-α and IL-6, then various concentrations of artemisinin were administrated to observe its dose-dependent inhibitory effect, and artemisinin were also added at different time to observe the time-dependent effect.Contents of cytokines in culture supernatant were detected by ELISA.RESULTS: Different concentrations of artemisinin decreased the death of mice challenged with CpG DNA, and the mortality were dropped from 80% to 10% (P<0.01). 20 g°ml-1 artemisinin significantly inhibited the release of TNF-αand IL-6 from RAW 264.7 induced by CpG DNA.The cytokines was markedly inhibited when artemisinin was added first (P<0.01).And the release of TNF-αand IL-6 were obviously suppressed if the cells were stimulated by CpG DNA prior to artemisin (P<0.01).CONCLUSION: Atemisinin has a protective effect on mice challenged with CpG DNA, and it can obviously inhibit pro-inflammatory cytokines released from RAW 264.7 in a dose- and time-dependent manner.

Key words: artemisinin, SIRS, CpG DNA, pro-inflammatory cytokines, LPS

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