双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应

覃万翔; 罗敏; 石英; 崔剑; 聂发传; 骆世芳; 贺桂琼; 汪克建

doi:10.16016/j.1000-5404.201706124

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双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应

基础医学 | 更新时间：2026-01-09

- 双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应
- Inhibitory effects of dihydroartemisinin on LPS-induced inflammatory response in BV-2 microglial cells
- 第三军医大学学报 2017年39卷第22期页码：2189-2194
- 作者机构：
  
  1.400016 重庆，重庆医科大学神经科学研究中心
  2.400038 重庆，第三军医大学西南医院疼痛科
- 作者简介：
  
  [ 汪克建, E-mail: wangkejian@cqmu.edu.cn WANG Kejian, E-mail: wangkejian@cqmu.edu.cn
- 基金信息：
  
  国家自然科学基金面上项目(81371221);重庆市基础与前沿研究计划项目(CSTC2016jcyjA0069);重庆市教委科学技术研究项目(KJ130317);重庆市渝中区科技项目(20130132)
- DOI：10.16016/j.1000-5404.201706124
  中图分类号： R282.71;R322.8;R364.5
- 收稿：2017-06-22，
  
  修回：2017-08-17，
  
  纸质出版：2017-11-30
- 稿件说明：
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覃万翔, 罗敏, 石英, 等. 双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应[J]. 第三军医大学学报, 2017,39(22):2189-2194.

Wanxiang QIN, Min LUO, Ying SHI, et al. Inhibitory effects of dihydroartemisinin on LPS-induced inflammatory response in BV-2 microglial cells[J]. Journal of Third Military Medical University, 2017, 39(22): 2189-2194.
覃万翔, 罗敏, 石英, 等. 双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应[J]. 第三军医大学学报, 2017,39(22):2189-2194. DOI： 10.16016/j.1000-5404.201706124.

Wanxiang QIN, Min LUO, Ying SHI, et al. Inhibitory effects of dihydroartemisinin on LPS-induced inflammatory response in BV-2 microglial cells[J]. Journal of Third Military Medical University, 2017, 39(22): 2189-2194. DOI： 10.16016/j.1000-5404.201706124.

摘要

目的

观察双氢青蒿素(dihydroartemisinin，DHA)对脂多糖(lipopolysaccharide，LPS)诱导的BV-2小胶质细胞神经炎症反应的影响及其机制。

方法

LPS诱导BV-2小胶质细胞活化建立炎症模型，用不同浓度DHA(0.5、1、2、4 μmol/L)处理细胞，CCK-8检测细胞活性；选取1 μmol/L DHA干预细胞，倒置相差显微镜下观察细胞形态的变化；RT-PCR检测iNOS、IL-1β、IL-6、TNF-α基因表达水平；ELISA检测培养基中IL-1β、IL-6、TNF-α的表达水平；Western blot检测NF-κB、IκBα及TLR4的蛋白表达。

结果

低剂量的DHA(

2 μmol/L)对BV-2细胞活性无明显影响(

0.05)，DHA可抑制LPS引起的BV-2细胞形态变化，DHA抑制活化的BV-2细胞iNOS、IL-1β、IL-6、TNF-α mRNA的表达(

0.01)，减少IL-1β、IL-6、TNF-α炎症因子释放(

0.01)，明显降低TLR4的蛋白表达，减少细胞质内IκBα的表达，并抑制NF-κB向核内移位(

0.01)。

结论

DHA可能通过作用于TLR4/NF-κB通路，抑制LPS诱导的BV-2小胶质细胞NF-κB的激活，从而抑制炎症因子的产生，发挥抗炎作用。

Abstract

Objective

To investigate the inhibitory effect of dihydroartemisinin (DHA) on lipopolysaccharide (LPS)-induced inflammatory response in BV-2 microglial cells.

Methods

Inflammatory model was established by exposure of BV-2 cells to LPS for 24 h. Then after the cells were treated with different concentrations of DHA (0.5

2 and 4 μmol/L)

cell viability was tested with CCK-8 assay. The cell morphology was observed under inverted phase contrast microscope after the inflammatory cell model under the treatment of a harmless concentration (1 μmol/L) of DHA

The mRNA expression of iNOS

IL-1β

IL-6 and TNF-α was measured by RT-PCR. The contents of TNF-α

IL-1β and IL-6 in the supernatant were detected by ELISA. The expression of the nuclear NF-κB (p65)

IκBα

and TLR4 were analyzed by Western blotting.

Results

DHA showed no significant effect on cell viability when the concentration was lower than 2 μmol/L (

0.05). DHA inhibited the cell morphological changes induced by LPS. DHA treatment resulted in the decreases in the mRNA expression levels of iNOS

IL-1β

IL-6 and TNF-α (

0.01)

the production of pro-inflammatory cytokines IL-1β

IL-6

TNF-α

the protein levels of TLR4

intracytoplasmic IκBα and the nuclear translocation of NF-κB p65 (

0.01).

Conclusion

DHA inhibits the inflammatory responses

activation of NF-κB of BV-2 microglial cells induced by LPS

and thus suppresses the production of pro-inflammatory cytokines

via

TLR4/NF-κB signaling pathway.

关键词

Keywords

references

张婷, 曾庆桦, 刘滢, 等.胰淀素在痴呆小鼠和正常小鼠脑内的分布和表达变化[J].第三军医大学学报, 2016, 38(3):258-263.DOI:10.16016/j.1000-5404.201506040.

ZHANG T, ZENG Q H, LIU Y, et al .Distribution and expression of amylin in brain of Alzheimer's disease and normal mice[J ] . J Third Mil Med Univ, 2016, 38(3): 258-263. DOI: 10.16016/j.1000-5404.201506040.

FU W, PATEL A, JHAMANDAS J H. Amylin receptor: a common pathophysiological target in Alzheimer's disease and diabetes mellitus[J]. Front Aging Neurosci, 2013, 5: 42. DOI: 10.3389/fnagi.2013.00042.

WANG Y, HUANG Z, WANG L, et al . The anti-malarial artemisinin inhibits pro-inflammatory cytokines via the NF-κB canonical signaling pathway in PMA-induced THP-1 monocytes[J ] . Int J Mol Med, 2011, 27(2): 233-241. DOI:10.3892/ijmm.2010.580..

JIANG L B, MENG D H, LEE S M, et al .Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway[J ] . Sci Rep, 2016, 6: 38979. DOI: 10.1038/srep38979..

尹怡, 曹鎏, 李飞, 等.双氢青蒿素促进胶质瘤GL261细胞的凋亡[J].第三军医大学学报, 2013, 35(12): 1179-1182. DOI: 10.16016/j.1000-5404.2013.12.002.

YIN Y, CAO L, LI F, et al .Dihydroartemisinin induces apoptosis inGL261 glioma cells[J ] . J Third Mil Med Univ, 2013, 35(12): 1179-1182. DOI: 10.16016/j.1000-5404.2013.12.002.

HOU J, WANG D, ZHANG R, et al . Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action[J ] . Clin Cancer Res, 2008, 14(17): 5519-5530. DOI: 10.1158/1078-0432.CCR-08-0197..

D'ANGELO J G, BORDÓN C, POSNER G H, et al .Artemisinin derivatives inhibit toxoplasma gondii in vitro at multiple steps in the lytic cycle[J ] . J Antimicrob Chemother, 2009, 63(1): 146-150. DOI: 10.1093/jac/dkn451..

SHI C, LI H, YANG Y, et al . Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives[J ] . Mediators Inflamm, 2015, 2015: 435713. DOI:10.1155/2015/435713.

YANG C, NIU S, YU L, et al . The aqueous extract of angelica sinensis, a popular Chinese herb, inhibits wear debris-induced inflammatory osteolysis in mice[J ] . J Surg Res, 2012, 176(2): 476-483. DOI:10.1016/j.jss.2011.08.011.

HOU L F, HE S J, LI X, et al . SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development[J ] . PLoS ONE, 2012, 7(2): e32424. DOI:10.1371/journal.pone.0032424.

HENEKA M T. Inflammasome activation and innate immunity in Alzheimer's disease[J]. Brain Pathol, 2017, 27(2): 220-222. DOI:10.1111/bpa.12483.

薛鑫, 陈星星, 王冠, 等.甲酰基肽受体1对BV-2细胞迁移的影响及机制的体外研究[J].第三军医大学学报, 2016, 38 (1): 44-49. DOI: 10.16016/j.1000-5404.201504153.

XUE X, CHEN X X, WANG G, et al . Formyl peptide receptor 1 promotes migration in mouse microglial cell line BV-2[J ] . J Third Mil Med Univ, 2016, 38 (1): 44-49. DOI: 10.16016/j.1000-5404.201504153.

PERRY V H, TEELING J. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration[J]. Semin Immunopathol, 2013, 35(5): 601-612. DOI: 10.1007/s00281-013-0382-8.

DOU C, DING N, XING J, et al . Dihydroartemisinin attenuates lipopolysaccharide-induced osteoclastogenesis and bone loss via the mitochondria-dependent apoptosis pathway[J ] . Cell Death Dis, 2016, 7: e2162. DOI:10.1038/cddis.2016.69..

喻婉莹, 阚伟娟, 于鹏霞, 等.青蒿素和二氢青蒿素的抗炎作用及机制[J].中国中药杂志, 2012, 37(17):2618-2621.

YU W Y, KAN W J, YU P X, et al . Anti- inflammatory effect and mechanism of artemisinin and dihydroartemisinin[J ] . China J Chin Materia Medica, 2012, 37(17): 2618-2621.

HU W, CHEN S S, ZHANG J L, et al . Dihydroartemisinin induces autophagy by suppressing NF-κB activation[J ] . Cancer Lett, 2014, 343(2): 239-248. DOI: 10.1016/j.canlet.2013.09.035.

DONG F, ZHOU X, LI C, et al . Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis[J ] . Cancer Biol Ther, 2014, 15(11): 1479-1488. DOI: 10.4161/15384047.2014.955728..

ZHAO C, GAO W, CHEN T. Synergistic induction of apoptosis in A549 cells by dihydroartemisinin and gemcitabine[J]. Apoptosis, 2014, 19(4): 668-681. DOI: 10.1007/s10495-013-0953-0.

陈亚星, 袁继超, 刘伟, 等.莱菔硫烷抑制LPS诱导的小鼠星形胶质细胞增殖[J].第三军医大学学报, 2017, 39(5): 407-412. DOI: 10.16016/j.1000-5404.201609133.

CHEN Y X, YUAN J C, LIU W, et al .Sulforaphane inhibits astrocyte proliferation by induced LPS in mice[J ] . J Third Mil Med Univ, 2017, 39(5): 407-412. DOI: 10.16016/j.1000-5404.201609133.

BADSHA H H, ALI T, KIM M O. Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway[J ] . Sci Rep, 2016, 6: 24493. DOI: 10.1038/srep24493.

DOU W, ZHANG J, SUN A, et al . Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling[J ] . Br J Nutr, 2013, 110(4): 599-608. DOI: 10.1017/S0007114512005594..

ZHANG Y, LU Y, MA L, et al . Activation of vascular endothelial growth factor receptor-3 in macrophages restrains TLR4-NF-κB signaling and protects against endotoxin shock[J ] . Immunity, 2014, 40(4): 501-514. DOI: 10.1016/j.immuni.2014.01.013.

JACOBS M D, HARRISON S C. Structure of an Ikappa B alpha/NF-kappa B complex[J]. Cell, 1998, 95(6): 749-758. DOI:10.1016/s0092-8674(00)81698-0.

YAZDI S, DURDAGI S, NAUMANN M, et al .Structural modeling of the N-terminal signal-receiving domain of IκBα[J ] .Front Mol Biosci, 2015, 2:32.DOI:10.3389/fmolb.2015.00032.

LI W D, DONG Y J, TU Y Y, et al . Dihydroarteannuin ameliorates lupussymptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation[J ] . Int Immunopharmacol, 2006, 6(8): 1243-1250. DOI:10.1016/j.intimp.2006.03.004.

YANG D, YUAN W, LV C, et al . Dihydroartemisininsu-presses inflammation and fibrosis in bleomycine-induced pulmonary fibrosis in rats[J ] . Int J Clin Exp Pathol, 2015, 8(2): 1270-1281.

ZHANG Z, GUO M, ZHAO S, et al . ROS-JNK1/2-dependent activation of autophagy is required for the induction of anti-inflammatory effect of dihydroartemisinin in liver fibrosis[J ] . Free Radic Biol Med, 2016, 101: 272-283. DOI:10.1016/j.freeradbiomed.2016.10.498.

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