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预处理 S-亚硝基谷胱甘肽通过抑制炎症、氧化和细胞凋亡来减轻大鼠脓毒症急性肾损伤。

Pretreatment with S-Nitrosoglutathione Attenuates Septic Acute Kidney Injury in Rats by Inhibiting Inflammation, Oxidation, and Apoptosis.

机构信息

Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, Zhejiang Province, China.

出版信息

Biomed Res Int. 2021 Feb 1;2021:6678165. doi: 10.1155/2021/6678165. eCollection 2021.

Abstract

OBJECTIVE

We aimed to investigate the protective effect of s-nitrosoglutathione (SNG) pretreatment on acute kidney injury (AKI) in septic rats.

METHODS

We constructed a rat model of sepsis by cecal ligation and puncture and observed the survival of the rats. We obtained kidney and blood samples from rats, observed the pathological damage to the kidney tissues, and evaluated kidney function and the expression levels of inflammatory factors. We also detected the expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the kidneys by immunohistochemistry and evaluated the apoptosis of kidney tubular epithelial cells (KTEC) by TUNEL.

RESULTS

Pretreatment with SNG significantly reduced the mortality of septic rats, attenuated kidney pathological damage, and decreased the levels of serum creatinine, plasma neutrophil gelatinase-associated lipocalin, and plasma kidney injury molecule-1. Moreover, SNG pretreatment decreased the levels of TNF- and IL-1 in serum and kidney and reduced the expressions of NO, iNOS, PGE2, and COX-2 in the kidneys. Furthermore, pretreatment with SNG significantly reduced the apoptotic rate of KTEC and decreased the levels of caspase-3 and Bax mRNA, but increased the level of Bcl-2 mRNA.

CONCLUSION

Pretreatment with SNG has a protective effect on AKI in septic rats, and the specific mechanisms are related to inhibition of inflammation, oxidation, and apoptosis.

摘要

目的

本研究旨在探讨 S-亚硝基谷胱甘肽(SNG)预处理对脓毒症大鼠急性肾损伤(AKI)的保护作用。

方法

采用盲肠结扎穿孔法构建脓毒症大鼠模型,观察大鼠的生存情况。取大鼠肾脏和血液样本,观察肾脏组织的病理损伤,评估肾功能和炎症因子的表达水平。采用免疫组织化学法检测肾脏中诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达,并用 TUNEL 法评估肾小管上皮细胞(KTEC)的凋亡情况。

结果

SNG 预处理可显著降低脓毒症大鼠的死亡率,减轻肾脏的病理损伤,降低血清肌酐、血浆中性粒细胞明胶酶相关脂质运载蛋白和血浆肾损伤分子-1的水平。此外,SNG 预处理可降低血清和肾脏中 TNF-α和 IL-1 的水平,降低肾脏中 NO、iNOS、PGE2 和 COX-2 的表达。此外,SNG 预处理可显著降低 KTEC 的凋亡率,降低 caspase-3 和 BaxmRNA 的水平,增加 Bcl-2mRNA 的水平。

结论

SNG 预处理对脓毒症大鼠的 AKI 具有保护作用,其具体机制与抑制炎症、氧化和凋亡有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe8/7872741/70ecfbff1a5b/BMRI2021-6678165.001.jpg

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