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γ-氨基丁酸通过上调B型受体减轻脂多糖诱导的小鼠急性肺损伤。

γ-aminobutyric acid alleviates LPS-induced acute lung injury in mice through upregulating type B receptors.

作者信息

Yang Jing, Li Na, Zhen Yuanyuan, Huang Qikun

机构信息

Pediatric Department, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.

出版信息

Arch Med Sci. 2019 Nov 25;19(4):1116-1123. doi: 10.5114/aoms.2019.89984. eCollection 2023.

DOI:10.5114/aoms.2019.89984
PMID:37560718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10408013/
Abstract

INTRODUCTION

In recent years, studies have shown that GABA has a certain therapeutic effect on acute lung injury (ALI), but its specific mechanism has not been fully elucidated. The study was designed to investigate the protective effect and mechanism of γ-aminobutyric acid (GABA) on ALI induced by lipopolysaccharide (LPS) in mice.

MATERIAL AND METHODS

C57BL/6 mice were randomly divided into a control group, LPS group, LPS + GABA (10 mg/kg) group and LPS + dexamethasone (Dex, 5 mg/kg) group. The survival rate of each group was observed at different time points after modeling. The levels of tumor necrosis factor α (TNF-α), interleukin (IL) 1β, 10, myeloperoxidase (MPO) and the cell count and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Lung histopathology and the expression of GABA receptors were observed by HE staining and immunohistochemistry respectively. Lung water content was assessed by wet-dry weight ratio.

RESULTS

GABA could significantly improve the survival rate and prolong the survival time of animals, alleviate the degree of inflammatory injury and pulmonary edema, reduce the content of MPO, down-regulate the levels of pro-inflammatory cytokines IL-1β and TNF-α, and up-regulate the expression of anti-inflammatory cytokine IL-10. Moreover, GABA could significantly decrease the expression of type A receptors and enhance type B receptors.

CONCLUSIONS

GABA can effectively alleviate ALI induced by LPS in mice, and its effect may be related to the upregulation of type B receptors.

摘要

引言

近年来,研究表明γ-氨基丁酸(GABA)对急性肺损伤(ALI)具有一定的治疗作用,但其具体机制尚未完全阐明。本研究旨在探讨γ-氨基丁酸(GABA)对脂多糖(LPS)诱导的小鼠ALI的保护作用及机制。

材料与方法

将C57BL/6小鼠随机分为对照组、LPS组、LPS + GABA(10 mg/kg)组和LPS + 地塞米松(Dex,5 mg/kg)组。建模后在不同时间点观察各组小鼠的存活率。检测肿瘤坏死因子α(TNF-α)、白细胞介素(IL)1β、10、髓过氧化物酶(MPO)水平以及支气管肺泡灌洗液(BALF)中的细胞计数和蛋白浓度。分别通过HE染色和免疫组织化学观察肺组织病理学及GABA受体的表达。通过湿干重比评估肺含水量。

结果

GABA可显著提高动物存活率、延长存活时间,减轻炎症损伤和肺水肿程度,降低MPO含量,下调促炎细胞因子IL-1β和TNF-α水平,上调抗炎细胞因子IL-10的表达。此外,GABA可显著降低A型受体的表达并增强B型受体的表达。

结论

GABA可有效减轻LPS诱导的小鼠ALI,其作用可能与上调B型受体有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a353/10408013/19697a96c25f/AMS-19-4-113328-g005.jpg
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