Mechanism of NLRP3 inflammasome promoting sepsis-induced acute kidney injury

ZHU Min-jie; HE Qi; MIAO Ying-ying

doi:10.11659/jjssx.06E022098

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Mechanism of NLRP3 inflammasome promoting sepsis-induced acute kidney injury

Basic Research | 更新时间：2023-05-26

- Mechanism of NLRP3 inflammasome promoting sepsis-induced acute kidney injury
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 32, Issue 5, Pages: 376-381(2023)
- 作者机构：
  
  邯郸市中心医院肾内二科，河北邯郸 056002
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.06E022098
  CLC： R692
- Published：25 May 2023，
  
  Received：30 June 2022，
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朱敏杰,何琦,苗盈盈.NLRP3炎性小体促进脓毒症致急性肾损伤的机制研究[J].局解手术学杂志,2023,32(05):376-381.

ZHU Min-jie,HE Qi,MIAO Ying-ying.Mechanism of NLRP3 inflammasome promoting sepsis-induced acute kidney injury[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(05):376-381.
朱敏杰,何琦,苗盈盈.NLRP3炎性小体促进脓毒症致急性肾损伤的机制研究[J].局解手术学杂志,2023,32(05):376-381. DOI： 10.11659/jjssx.06E022098.

ZHU Min-jie,HE Qi,MIAO Ying-ying.Mechanism of NLRP3 inflammasome promoting sepsis-induced acute kidney injury[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(05):376-381. DOI： 10.11659/jjssx.06E022098.

摘要

目的

探讨NOD样受体家族热蛋白结构域相关蛋白3(NLRP3)炎性小体在脓毒症致急性肾损伤中的作用及其可能的机制。

方法

将40只SD大鼠随机分为对照组、模型组、MCC950组和Ac-YVAD-CMK组，每组10只。采用盲肠结扎穿刺术建立脓毒症大鼠模型，MCC950组和Ac-YVAD-CMK组大鼠造模后分别腹腔注射MCC950 10 mg/kg和Ac-YVAD-CMK 5 mg/kg，对照组大鼠仅探查肓肠。ELISA法检测尿素氮、肌酐、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、IL-1β、IL-18含量；Western blot检测肾损伤分子-1（KIM-1）、NLRP3、凋亡相关斑点样蛋白（ASC)、Caspase-1、消皮素D（GSDMD）和半乳糖结合蛋白Galectin-3表达；HE染色观察大鼠肾组织病理学变化；PAS染色观察大鼠肾小管损伤情况。

结果

与对照组相比，模型组大鼠肾组织病理学评分、尿素氮、肌酐、NGAL、IL-1β、IL-18、糖原沉积水平及KIM-1、NLRP3、ASC、Caspase-1、GSDMD和Galectin-3蛋白表达显著升高（

0.05）。与模型组相比，MCC950组和Ac-YVAD-CMK组大鼠肾组织病理学评分、尿素氮、肌酐、NGAL、IL-1β和IL-18、糖原沉积水平及KIM-1、Caspase-1、GSDMD和Galectin-3蛋白表达显著降低（

0.05）。

结论

NLRP3炎性小体通过诱导细胞焦亡和上调Galectin-3表达，促进脓毒症大鼠急性肾损伤。

Abstract

Objective

To explore the effect of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in sepsis-induced acute kidney injury and its potential mechanism.

Methods

Forty SD rats were randomly divided into the control group

model group

MCC950 group

and Ac-YVAD-CMK group

with 10 rats in each group.A sepsis-induced rat model was established by cecal ligation and puncture surgery

rats in the MCC950 group and Ac-YVAD-CMK group gave intraperitoneal injection with 10 mg/kg of MCC950 and 5 mg/kg of Ac-YVAD-CMK

respectively after modeling

and rats in the control group only gave cecal exploration.ELISA was used to detect the levels of blood urea nitrogen

creatinine

neutrophil gelatinase-associated lipocalin (NGAL)

IL-1β

and IL-18.Western blot was used to detect the protein expression of kidney injury molecule-1 (KIM-1)

NLRP3

apoptosis-associated speck-like protein containing a CARD (ASC)

Caspase-1

gasdermin D (GSDMD) and Galectin-3.Histopathological changes in rat kidney tissues were observed by HE staining

and renal tubular injury was observed by PAS staining.

Results

Compared with the control group

the histopathological score of renal tissues

blood urea nitrogen

creatinine

NGAL

IL-1β

IL-18

glycogen storage level

and protein expression of KIM-1

NLRP3

ASC

Caspase-1

GSDMD and Galectin-3 in the model group were significantly increased (

0.05).Compared with the model group

the histopathological score of renal tissues

blood urea nitrogen

creatinine

NGAL

IL-1β

IL-18

glycogen storage level

and protein expression of KIM-1

NLRP3

Caspase-1

GSDMD and Galectin-3 in the MCC950 group and the Ac-YVAD-CMK group were significantly decreased (

0.05).

Conclusion

NLRP3 inflammasome promotes sepsis-induced acute kidney injury in rats by inducing pyroptosis and upregulating Galectin-3 expression.

关键词

NLRP3炎性小体脓毒症急性肾损伤细胞焦亡Galectin-3

Keywords

NLRP3inflammasomesepsisacute renal injurypyroptosisGalectin-3

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