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S-亚硝基谷胱甘肽预处理对脓毒症大鼠急性肺损伤的保护作用

Protective effect of S-nitrosoglutathione pretreatment on acute lung injury in septic rats.

作者信息

Wang Zhou-Feng, Yang Yu-Min, Fan Heng

机构信息

Department of Respiratory and Critical Care, Ningbo First Hospital Longshan Hospital Medical and Health Group, Ningbo, Zhejiang Province, P.R China.

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

出版信息

Iran J Basic Med Sci. 2020 Aug;23(8):1059-1064. doi: 10.22038/ijbms.2020.43590.10240.

DOI:10.22038/ijbms.2020.43590.10240
PMID:32952953
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7478255/
Abstract

OBJECTIVES

To investigate the protective effect of S-nitrosoglutathione (SNG) pretreatment on acute lung injury (ALI) in septic rats.

MATERIALS AND METHODS

We constructed a rat model of sepsis by cecal ligation and perforation (CLP), and randomly divided into Sham, CLP, and CLP+SNG (0.25 and 0.5 mg/kg) groups. We used H&E staining and lung wet/dry ratio to assess the severity of lung injury, detected the levels of protein and cells in bronchoalveolar lavage fluid (BALF) and the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA in the lung tissue, and assessed the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in the lung tissue.

RESULTS

A rat model of sepsis was successfully constructed by CLP, and pretreatment of SNG significantly increased the survival of septic rats (<0.001) and decreased the lung tissue injury scores (<0.001) and lung wet/dry ratio (<0.01) in a dose-dependent manner. Furtherly, SNG pretreatment significantly reduced the number of total cells, total protein, neutrophils, and lympholytes (all <0.001) in BALF, and which also decreased the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA (all <0.001) in the lungs of CLP-induced rats. Moreover, pretreatment of SNG significantly increased the levels of anti-oxidant enzymes GSH, SOD, GSH-Px, and catalase (all <0.001) in the lung tissue of septic rats.

CONCLUSION

SNG pretreatment has a protective effect on ALI in septic rats, and the specific mechanism may be related to anti-endotoxic, anti-inflammatory, and anti-oxidative properties.

摘要

目的

探讨S-亚硝基谷胱甘肽(SNG)预处理对脓毒症大鼠急性肺损伤(ALI)的保护作用。

材料与方法

通过盲肠结扎穿孔术(CLP)构建大鼠脓毒症模型,并随机分为假手术组、CLP组和CLP+SNG(0.25和0.5mg/kg)组。采用苏木精-伊红(H&E)染色和肺组织湿/干比评估肺损伤严重程度,检测支气管肺泡灌洗液(BALF)中蛋白质和细胞水平以及肺组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、Toll样受体4(TLR4)mRNA和核因子-κB p65(NF-κB p65)mRNA水平,并评估肺组织中谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶水平。

结果

通过CLP成功构建了大鼠脓毒症模型,SNG预处理显著提高了脓毒症大鼠的生存率(<0.001),并以剂量依赖方式降低了肺组织损伤评分(<0.001)和肺湿/干比(<0.01)。此外,SNG预处理显著降低了BALF中总细胞、总蛋白、中性粒细胞和淋巴细胞数量(均<0.001),同时也降低了CLP诱导大鼠肺组织中TNF-α、IL-1β、TLR4 mRNA和NF-κB p65 mRNA水平(均<0.001)。而且,SNG预处理显著提高了脓毒症大鼠肺组织中抗氧化酶GSH、SOD、GSH-Px和过氧化氢酶水平(均<0.001)。

结论

SNG预处理对脓毒症大鼠ALI具有保护作用,其具体机制可能与抗内毒素、抗炎和抗氧化特性有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/cebf59866384/IJBMS-23-1059-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/0859ddd2d290/IJBMS-23-1059-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/ef86dac2b739/IJBMS-23-1059-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/9aa436c1b470/IJBMS-23-1059-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/cebf59866384/IJBMS-23-1059-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/0859ddd2d290/IJBMS-23-1059-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/ef86dac2b739/IJBMS-23-1059-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/9aa436c1b470/IJBMS-23-1059-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7478255/cebf59866384/IJBMS-23-1059-g004.jpg

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