Naoxintong Inhibits LPS Induced BV2 Cell Pyroptosis by NLRP3/Caspase-1 Signaling Pathway

Dong WANG; Xiao-hui SU; Ming-zhu QI; Yan-qiu WANG; Xiang-ying KONG; Na LIN

doi:10.13422/j.cnki.syfjx.20201037

您当前的位置：

首页 >

文章列表页 >

Naoxintong Inhibits LPS Induced BV2 Cell Pyroptosis by NLRP3/Caspase-1 Signaling Pathway

Pharmacology | 更新时间：2021-02-09

- Naoxintong Inhibits LPS Induced BV2 Cell Pyroptosis by NLRP3/Caspase-1 Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 10, Pages: 29-34(2020)
- 作者机构：
  
  1.贵州中医药大学，贵阳　 550025
  2.中国中医科学院　中药研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201037
  CLC： R2-0; R289; R285.5
- Received：23 December 2019，
  
  Published Online：06 February 2020，
  
  Published：20 May 2020
- 稿件说明：
移动端阅览
Dong WANG, Xiao-hui SU, Ming-zhu QI, et al. Naoxintong Inhibits LPS Induced BV2 Cell Pyroptosis by NLRP3/Caspase-1 Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(10): 29-34.
DOI：

Dong WANG, Xiao-hui SU, Ming-zhu QI, et al. Naoxintong Inhibits LPS Induced BV2 Cell Pyroptosis by NLRP3/Caspase-1 Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(10): 29-34. DOI： 10.13422/j.cnki.syfjx.20201037.

摘要

目的：

探索脑心通醇提物对脂多糖(LPS)诱导的小胶质细胞BV2焦亡的影响，并通过NOD样受体热蛋白结构域3(NLRP3)/半胱氨酸蛋白酶-1(Caspase-1)通路阐释其可能的作用机制。

方法：

LPS(1 mg·L

-1

)体外诱导BV2细胞的同时，加入不同质量浓度脑心通醇提物(2，10，50 mg·L

-1

)干预后，分别采用MTS法检测细胞活性，实时荧光定量PCR(Real-time PCR)检测白细胞介素-1

(IL-1

)，肿瘤坏死因子-

(TNF-

)和NLRP3的mRNA水平；免疫荧光法检测NLRP3蛋白表达的情况；蛋白免疫印迹法(Western blot)检测NLRP3/Caspase-1通路关键蛋白表达。

结果：

与空白组比较，LPS(1 mg·L

-1

)能明显降低BV2细胞活性，显著升高IL-1

，TNF-

及NLRP3 mRNA表达水平(

0.01)，且可提升NLRP3蛋白表达水平以及Caspase-1剪切体和前体蛋白的比值(Caspase-1 p20/Caspase-1)。与LPS组比较，脑心通醇提物(2，10，50 mg·L

-1

)干预后，逆转了LPS导致的细胞活性降低(

0.01)，50 mg·L

-1

脑心通醇提物可显著降低IL-1

，TNF-

及NLRP3 mRNA表达水平(

0.05，

0.01)，显著降低LPS诱导的NLRP3的高表达以及Caspase-1 p20/Caspase-1(

0.01)。

结论：

脑心通能明显抑制LPS诱导的小胶质细胞焦亡，其作用机制与NLRP3/Caspase-1通路密切相关。

Abstract

Objective:

To explore the effect of Naoxintong ethanol extract (NXT) on pyroptosis of BV2 microglia cells induced by lipopolysaccharide (LPS)

and to explain the mechanism of pyroptosis based on NOD like receptor thermoprotein domain 3 (NLRP3)/cysteine-proteinase-1 (Caspase-1) pathway.

Method:

BV2 cells was treated with different concentrations of NXT(2

50 mg·L

-1

) after induced by LPS(1 mg·L

-1

)

in vitro

. Real-time PCR was used to detect mRNA expression of pro-inflammatory cytokine such as interleukin 1 beta (IL-1

)

tumor necrosis factor (TNF)-

and NLRP3.Western bolt and immunofluorescence were used to observe the protein expression of NLRP3/Caspase-1 signaling pathway.

Result:

Compared with control group

after LPS(1 mg·L

-1

) stimulation

BV2 cells viability was decreased. The mRNA expression levels of IL-1

TNF-

and NLRP3 were significantly elevated(

0.01)

the protein levels of NLRP3 and Caspase-1 p20/Caspase-1 were also increased. After given NXT(2

50 mg·L

-1

)

BV2 cells viability reversed which induced by LPS. Compared with LPS group

the mRNA expression of IL-1

TNF-

and NLRP3 reduced obviously with given 50 mg·L

-1

NXT (

0.05

0.01)

significantly inhibited NLRP3 high protein expression and Caspase-1 p20/Caspase-1 expression(

0.01).

Conclusion:

NXT can inhibit LPS induced pyroptosis of BV2 cells and the mechanism may closely related to NLRP3/Caspase-1 signaling pathway.

关键词

Keywords

references

曹冰倩，谭峰．细胞焦亡对脑梗死神经修复的影响 [J]．深圳中西医结合杂志， 2019 ， 29 ( 5 )： 179 - 182 .

赵清，杨丽玲，杜怡峰．步长脑心通对大鼠急性脑缺血再灌注小胶质细胞炎症反应和神经细胞凋亡的影响 [J]．山东大学学报：医学版， 2010 ， 48 ( 11 )： 46 - 49 .

D P ABULAFIA , J P DE RIVERO VACCARI , J D LOZANO , et al . Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice [J]. J Cereb Blood Flow Metab ， 2009 ， 29 ( 3 )： 534 - 544 .

赵涛，王一民，刘娜，等．从补阳还五汤到脑心通胶囊——脑心同治的思路探讨 [J]．世界中西医结合杂志， 2012 ， 7 ( 10 )： 900 - 903 .

何子龙，赵晔，张毅，等．脑心通胶囊肠吸收液保护过氧化氢致HPc2心肌细胞损伤的作用机制及有效药味筛选 [J]．中国实验方剂学杂志， 2019 ， 25 ( 4 )： 29 - 35 .

赵步长，赵涛，宋琳琳，等．脑心通胶囊的类阿司匹林作用及其在防治心脑血管疾病中的应用 [J]．中医杂志， 2016 ， 57 ( 15 )： 1337 - 1341 .

李伟霞，张书琦，赵艺丹，等．脑心通胶囊化学成分、药理作用及临床应用研究进展 [J]．中国中药杂志， 2018 ， 43 ( 10 )： 1998 - 2005 .

杨岳，李慧影，张璐莎，等．脑心通胶囊提取物通过增强CXCR4表达促进心脏干细胞迁移 [J]．天津中医药大学学报， 2016 ， 35 ( 2 )： 99 - 103 .

王陇德，刘建民，杨弋，等．我国脑卒中防治仍面临巨大挑战——《中国脑卒中防治报告2018》概要 [J]．中国循环杂志， 2019 ， 34 ( 2 )： 105 - 119 .

C J MURRAY , A D LOPEZ . Measuring the global burden of disease [J]. N Engl J Med ， 2013 ， 369 ( 5 )： 448 - 457 .

R LOZANO , M NAGHAVI , K FOREMAN , et al . Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 [J]. Lancet ， 2012 ， 380 ( 9859 )： 2095 - 2128 .

S PRABHAKARAN , A C CASTONGUAY , R GUPTA , et al . Complete reperfusion mitigates influence of treatment time on outcomes after acute stroke [J]. J Neurointerv Surg ， 2017 ， 9 ( 4 )： 366 - 369 .

唐标，邓常清．细胞焦亡与脑卒中 [J]．生理学报， 2018 ， 70 ( 1 )： 93 - 98 .

孙玉洁，张楠楠，赵萌．白藜芦醇对大鼠脑组织缺血再灌注过程中细胞焦亡的调控作用及对小胶质细胞NLRP3炎症小体、Caspase-1及ZO-1的影响 [J]．海南医学院学报， 2019 ， 25 ( 17 )： 1291 - 1294 .

Y WANG , X YAN , S MI et al . Naoxintong attenuates ischaemia/reperfusion injury through inhibiting NLRP3 inflammasome activation [J]. J Cell Mol Med ， 2017 ， 21 ( 1 )： 4 - 12 .

吴作敏，郭丽娜，王单单，等．黄芪-川芎药对治疗脑卒中的网络药理学研究 [J]．药物评价研究， 2019 ， 42 ( 9 )： 1749 - 1756 .

刘亚鹭，徐士欣，张军平，等．川芎-当归药对有效成分在缺血性脑卒中应用的研究进展 [J]．华西药学杂志， 2018 ， 33 ( 6 )： 550 - 553 .

M SONG , J RUAN , R ZHANG et al . Astragaloside IV ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPAR γ /NF- κ B/NLRP3 inflammasome axis [J]. Acta Pharmacol Sin ， 2018 ， 39 ( 10 )： 1559 - 1570 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of Congrong Zonggan Capsules in Improving Neuroinflammation and Cognitive Impairment in 5×FAD Mice Based on NF-κB/NLRP3 Signaling Pathway

Mechanism of Wenyang Jieyu Prescription in Regulating Activation of Mouse Hippocampal Microglia Based on JAK2/STAT3 Signaling Pathway

Modified Xiehuangsan Regulates Microglial Polarization and TLR4/MyD88/NF-κB Pathway to Treat Tic Disorders in Rats

Programmed Cell Death in Endometriosis and Traditional Chinese Medicine Intervention： A Review

Sesquiterpene ZH-13 from Aquilariae Lignum Resinatum Improves Neuroinflammation by Regulating JNK Phosphorylation

Related Author

ZHOU Yanru

GU Xinru

LIU Yuru

ZHANG Shun

LYU Yaozhong

WANG Zhenzhong

WANG Ying

GONG Zihan

Related Institution

State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture，Nanjing University of Chinese Medicine，Jiangsu Kanion Pharmaceutical Co. Ltd.

Kanion School of Chinese Materia Medica，Nanjing University of Chinese Medicine

Institute of Basic Theory for Chinese Medicine，China Academy of Chinese Medical Sciences

Ningxia Chinese Medicine Research Center

Hengshanqiao People's Hospital in Changzhou Economic Development Zone

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰