TXNIP激活NLRP3炎性小体在子痫前期发病中的作用

发布时间：2018-01-31 17:25

本文关键词： 硫氧还蛋白结合蛋白子痫前期缺氧复氧　出处：《重庆医科大学学报》2016年07期 　论文类型：期刊论文

【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 investigate thioredoxin-interacting protein. TXNP) activates nucleotide binding oligodeoxyribonucleotide domain like receptor protein 3 (NLR family pyrin domain containing 3). NLRP3) inflammatory corpuscles and preeclampsia. Methods: the placental tissues of 15 cases of PE and 15 cases of normal parturient were collected from December 2013 to June 2014 in the first affiliated Hospital of Chongqing Medical University. Western blot was used to detect the expression of TXNIP and NLRP3 in placenta. Human transformed primary extravillous trophoblast cell line. HTR 8 / SVneoa was cultured in vitro and divided into normal control group (n) and hypoxia reoxygenation / reoxygenation (H / R) group. H / R Scrambled si RNA(H/R si RNAs and H / R TXNIP si RNA(H/R siRNAs. After treatment, Western blot was used to detect the expression of TXNIP and NLRP3 protein. The activity of Caspase-1 was detected by cysteine protease-1 (Caspase-1) assay kit. TXNIP and NLRP3 were detected by Co-Immunoprecipitation Co-IP method. Apoptosis-associated speck-like protein containing CARD. Results the expression of NLRP3 and TXNIP in placenta of PE group was significantly higher than that of P0. 003 in group N. P0. 002; In the cell model, the expression of TXNIP and NLRP3 increased significantly after H- / R treatment, and the interaction between TXNIP and NLRP3 increased significantly. After inhibition of TXNIP, the expression of NLRP3 decreased significantly, and the level of ASC protein decreased significantly (P0. 001). Moreover, the inhibitory effect of H / R on invasion and value added ability was reduced by P0. 001. Conclusion the activation of NLRP3 inflammatory body mediated by TXNIP may play an important role in the pathogenesis of PE.
【作者单位】：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;
【基金】：国家自然科学基金面上资助项目(编号:81370732)
【分类号】：R714.244
【正文快照】： 子痫前期(preeclampsia,PE)是妊娠期特有的疾病[1],而妊娠本就是一个炎症过程,母胎界面的炎症失衡是导致PE发生的原因之一[2]。有研究证明,PE患者血液中白介素-1β(interleukin-1β,IL-1β)水平高于正常,而IL-1β的分泌与核苷酸结合寡聚化结构域样受体蛋白3(NLR family pyrin

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