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葛根素通过 NLRP3/Caspase-1/GSDMD 通路保护大鼠肾缺血再灌注损伤。

Puerarin protects renal ischemia-reperfusion injury in rats through NLRP3/Caspase-1/GSDMD pathway.

机构信息

The First Affiliated Hospital of Xinxiang Medical University - Department of Urology - Weihui - China.

The First Affiliated Hospital of Xinxiang Medical University - Life Science Center - Weihui - China.

出版信息

Acta Cir Bras. 2023 Dec 1;38:e387323. doi: 10.1590/acb387323. eCollection 2023.

DOI:10.1590/acb387323
PMID:38055404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10691188/
Abstract

PURPOSE: To observe the effect of puerarin on renal ischemia-reperfusion (I/R) injury in rats, and to explore its mechanism based on NLRP3/Caspase-1/GSDMD pathway. METHODS: Twenty-one Sprague-Dawley rats were divided into three groups: sham-operated group (sham), model group (RIRI), and puerarin treatment group (RIRI + Pue). The model of acute renal I/R injury was established by cutting the right kidney and clamping the left renal pedicle for 45 min. RESULTS: Renal function parameters were statistically significant in group comparisons. The renal tissue structure of rats in sham group was basically normal. Pathological changes were observed in the RIRI group. The renal pathological damage score and apoptosis rate in the RIRI group were higher than those in the sham group, and significantly lower in the RIRI + Pue group than in the RIRI group. Indicators of oxidative stress-superoxide dismutase, malondialdehyde, and glutathione peroxidase-were statistically significant in group comparisons. Compared with the sham group, the relative expressions of NLRP3, Caspase-1 and GSDMD proteins in the RIRI group were increased. Compared with the RIRI group, the RIRI + Pue group had significant reductions. CONCLUSIONS: Puerarin can inhibit the activation of NLRP3/Caspase-1/GSDMD pathway, inhibit inflammatory response and pyroptosis, and enhance the antioxidant capacity of kidney, thereby protecting renal I/R injury in rats.

摘要

目的：观察葛根素对大鼠肾缺血再灌注（I/R）损伤的影响，并基于 NLRP3/Caspase-1/GSDMD 通路探讨其作用机制。

方法：21 只 Sprague-Dawley 大鼠随机分为三组：假手术组（sham）、模型组（RIRI）和葛根素治疗组（RIRI+Pue）。通过切断右肾和夹闭左肾蒂 45 min 建立急性肾 I/R 损伤模型。

结果：组间比较肾功能参数有统计学意义。 sham 组大鼠的肾组织结构基本正常，RIRI 组观察到病理变化，RIRI 组的肾病理损伤评分和细胞凋亡率高于 sham 组，RIRI+Pue 组明显低于 RIRI 组。氧化应激指标超氧化物歧化酶、丙二醛和谷胱甘肽过氧化物酶在组间比较有统计学意义。与 sham 组相比，RIRI 组 NLRP3、Caspase-1 和 GSDMD 蛋白的相对表达量增加，RIRI+Pue 组明显降低。

结论：葛根素可抑制 NLRP3/Caspase-1/GSDMD 通路的激活，抑制炎症反应和细胞焦亡，增强肾脏的抗氧化能力，从而对大鼠肾 I/R 损伤起保护作用。

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本文引用的文献

[1]
Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats.

Acta Cir Bras. 2023

[2]
Puerarin inhibited oxidative stress and alleviated cerebral ischemia-reperfusion injury through PI3K/Akt/Nrf2 signaling pathway.

Front Pharmacol. 2023-5-22

[3]
Puerarin protects against sepsis-associated encephalopathy by inhibiting NLRP3/Caspase-1/GSDMD pyroptosis pathway and reducing blood-brain barrier damage.

Eur J Pharmacol. 2023-4-15

[4]
NLRP3 inflammasome: A potential therapeutic target to minimize renal ischemia/reperfusion injury during transplantation.

Transpl Immunol. 2022-12

[5]
Puerarin: A protective drug against ischemia-reperfusion injury.

Front Pharmacol. 2022-8-24

[6]
Puerarin ameliorates acute lung injury by modulating NLRP3 inflammasome-induced pyroptosis.

Cell Death Discov. 2022-8-18

[7]
Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK/PGC1α/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats.

Antioxidants (Basel). 2022-6-27

[8]
Puerarin attenuates LPS-induced inflammatory injury in gastric epithelial cells by repressing NLRP3 inflammasome-mediated apoptosis.

Toxicol In Vitro. 2022-6

[9]
NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression.

JCI Insight. 2021-12-8

[10]
Allicin ameliorates renal ischemia/reperfusion injury via inhibition of oxidative stress and inflammation in rats.

Biomed Pharmacother. 2021-10

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