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NLRP3炎性小体促进脓毒症致急性肾损伤的机制研究
Mechanism of NLRP3 inflammasome promoting sepsis-induced acute kidney injury
- 局解手术学杂志 2023年32卷第5期 页码：376-381
- 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：河北省医学科学研究课题计划项目(20200559)
DOI：10.11659/jjssx.06E022098
中图分类号： R692纸质出版日期：2023-05-25，
收稿日期：2022-06-30，
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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
2
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
2
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
2
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（
P
<
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（
P
<
0.05）。
结论
2
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
2
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
2
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
2
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 (
P
<
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 (
P
<
0.05).
Conclusion
2
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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