Effect of TXNIP mediated NLRP3 inflammasome activationon the pathogenesis of preeclampsia

Yang Yong; Zhang Hua

doi:10.13406/j.cnki.cyxb.000964

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Effect of TXNIP mediated NLRP3 inflammasome activationon the pathogenesis of preeclampsia

更新时间：2024-01-17

- Effect of TXNIP mediated NLRP3 inflammasome activationon the pathogenesis of preeclampsia
- Journal of Chongqing Medical University Vol. 41, Issue 7, Pages: 658-662(2016)
- 作者机构：
  
  重庆医科大学附属第一医院妇产科重庆医科大学中国-加拿大-新西兰联合母胎医学实验室
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.000964
  CLC： R714.244
- Published：2016，
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[1]杨勇,张华.TXNIP激活NLRP3炎性小体在子痫前期发病中的作用[J].重庆医科大学学报,2016,41(07):658-662.

Yang Yong, Zhang Hua. Effect of TXNIP mediated NLRP3 inflammasome activationon the pathogenesis of preeclampsia. [J]. Journal of Chongqing Medical University 41(7):658-662(2016)
[1]杨勇,张华.TXNIP激活NLRP3炎性小体在子痫前期发病中的作用[J].重庆医科大学学报,2016,41(07):658-662. DOI： 10.13406/j.cnki.cyxb.000964.

Yang Yong, Zhang Hua. Effect of TXNIP mediated NLRP3 inflammasome activationon the pathogenesis of preeclampsia. [J]. Journal of Chongqing Medical University 41(7):658-662(2016) DOI： 10.13406/j.cnki.cyxb.000964.

摘要

目的:探讨硫氧还蛋白结合蛋白（thioredoxin-interacting protein

TXNIP）激活核苷酸结合寡聚化结构域样受体蛋白3（NLR family pyrin domain containing 3

NLRP3）炎性小体与子痫前期（preeclampsia

PE）发病的关系。方法:收集重庆医科大学附属第一医院2013年12月至2014年6月分娩的15例PE和15例正常产妇的胎盘组织

应用Western blot检测胎盘中TXNIP与NLRP3的表达水平。以人绒毛外滋养细胞（human transformed primary extravillous trophoblast cell line

HTR8/SVneo）体外培养

分为正常对照组（N）组、缺氧复氧（hypoxia/reoxygenation

H/R）组、H/R+Scrambled si RNA（H/R+NC）组和H/R+TXNIP si RNA（H/R+si RNA）组。各组处理后使用Western blot检测细胞TXNIP和NLRP3蛋白表达水平

应用半胱氨酸蛋白酶-1（Caspase-1）活性检测试剂盒检测Caspase-1活性

应用蛋白质免疫共沉淀法（Co-Immunoprecipitation

Co-IP）检测TXNIP与NLRP3、凋亡相关的斑点样蛋白（apoptosis-associated speck-like protein containing CARD

ASC）之间的相互作用

并实时检测细胞侵袭与增殖。结果:TXNIP与NLRP3在PE组胎盘组织中的表达明显高于N组（P=0.003、P=0.002）;在细胞模型中

H/R处理后

TXNIP与NLRP3的表达明显升高（P=0.011、P=0.022）

相互之间作用明显加强;抑制TXNIP后

NLRP3表达明显降低（P=0.000）

ASC蛋白水平也明显下降（P=0.001）

而且降低H/R对侵袭与增值能力的抑制作用（P=0.001、P=0.038）。结论:TXNIP介导的NLRP3炎性体激活可能在PE发病中起作用。

Abstract

Objective:To explore the role of thioredoxin-interacting protein(TXNIP)mediated NLR family pyrin domain containing 3(NLRP3)inflammasome activation in the pathogenesis of preeclampsia(PE). Methods:Fifteen cases of early-onset PE and 15 cases of normal maternal placental tissue were collected in the First Affiliated Hospital of Chongqing Medical University from December2013 to June 2014. Western blot was used to detect the expression of TXNIP and NLRP3 in placenta. Human transformed primary extravillous trophoblast cell line(HTR8/SVneo)cells were used to establish the model of PE

which were divided into control group

hypoxia reoxygenation(H/R)group

H/R+Scrambled si RNA(H/R+NC)group and H/R+TXNIP si RNA(H/R+si RNA)group. After the treatment

expressions of TXNIP and NLRP3 were detected by Western blot;Caspase 1 activity was measured by Caspase-1 active detection kit;interaction between TXNIP and NLRP3 was tested by Co-IP;invasion and proliferation were detected by real-time cell analyzer instrument. Results:The expression of TXNIP and NLRP3 in placenta in PE group was obviously higher than that of normal group(P=0.003

P=0.002). In the cell model

H/R could increase the expression of TXNIP and NLRP3 obviously(P=0.000

P=0.001)

and interaction between TXNIP and NLRP3 was improved remarkably. After the inhibition of TXNIP

expression of NLRP3 was significantly reduced(P=0.000)

and ASC level was also declined obviously(P=0.001)

and the invasion and proliferation ability of H/R was decreased(P =0.001

P =0.038). Conclusion:TXNIP mediated NLRP3 inflammatory activation plays an important role in the pathogenesis of PE.

关键词

硫氧还蛋白结合蛋白子痫前期缺氧复氧

Keywords

thioredoxin-interacting proteinpreeclampsiahypoxia/reoxygenation

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