Liu Mei-Mei, Zhou Jin, Ji Dan, Yang Jun, Huang Yan-Ping, Wang Qi
Department of Histology and Embryology, Anhui Medical College, Hefei, Anhui 230601, P.R. China.
Exp Ther Med. 2021 Apr;21(4):303. doi: 10.3892/etm.2021.9734. Epub 2021 Jan 29.
The aim of the present study was to investigate the effects of diammonium glycyrrhizinate lipid ligand (DGLL) treatment on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in Sprague-Dawley rats. Rats orally received 30, 60 and 120 mg/kg DGLL. After 1 h, the rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection. After 6 h, lung injury was evaluated using hematoxylin and eosin staining techniques. Pulmonary edema was evaluated using lung wet-dry weight ratio, protein concentrations in the bronchoalveolar lavage fluid (BALF) and Evans blue (EB) extravasation in lung tissue. The expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in lung tissues were measured using ELISA. Myeloperoxidase (MPO) expression levels were detected by immunohistochemical staining. Western blotting was used to measure the expression level changes of intercellular adhesion molecule (ICAM)-1, as well as adherent and tight junction proteins, including vascular endothelial (VE)-cadherin, zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM)-1 that were associated with pulmonary inflammation and microvascular permeability. DGLL treatment significantly alleviated ALI induced by LPS, which was demonstrated by reduction of MPO-positive cells and expression levels of TNF-α, IL-1β and ICAM-1 in rat lung tissues. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and reduced EB extravasation. DGLL also reversed the reduced expression of VE-cadherin and tight junction proteins, including ZO-1, occludin and JAM-1 in the lung tissues caused by LPS. In conclusion, DGLL exhibits a protective effect on LPS-induced rat ALI, which is associated with the inhibition of inflammatory cell infiltration and microvascular barrier disruption. The present results provide a theoretical basis for the application of DGLL for the potential clinical treatment of ALI.
本研究旨在探讨甘草酸二铵脂质配体（DGLL）治疗对脂多糖（LPS）诱导的Sprague-Dawley大鼠急性肺损伤（ALI）和肺水肿的影响。大鼠口服给予30、60和120 mg/kg DGLL。1小时后，通过腹腔注射LPS（10 mg/kg）建立大鼠ALI模型。6小时后，使用苏木精-伊红染色技术评估肺损伤。使用肺湿干重比、支气管肺泡灌洗液（BALF）中的蛋白质浓度和肺组织中的伊文思蓝（EB）外渗来评估肺水肿。使用酶联免疫吸附测定（ELISA）测量肺组织中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β的表达水平。通过免疫组织化学染色检测髓过氧化物酶（MPO）表达水平。蛋白质印迹法用于测量细胞间黏附分子（ICAM）-1以及与肺部炎症和微血管通透性相关的黏附及紧密连接蛋白的表达水平变化，这些蛋白包括血管内皮（VE）-钙黏蛋白、闭锁小带（ZO）-1、闭合蛋白和连接黏附分子（JAM）-1。DGLL治疗显著减轻了LPS诱导的ALI，这通过大鼠肺组织中MPO阳性细胞以及TNF-α、IL-1β和ICAM-1表达水平的降低得以证明。此外，DGLL消除了LPS诱导的肺水肿，降低了BALF中的蛋白质浓度并减少了EB外渗。DGLL还逆转了LPS导致的肺组织中VE-钙黏蛋白和紧密连接蛋白（包括ZO-1、闭合蛋白和JAM-1）表达降低的情况。总之，DGLL对LPS诱导的大鼠ALI具有保护作用，这与抑制炎症细胞浸润和微血管屏障破坏有关。本研究结果为DGLL在ALI潜在临床治疗中的应用提供了理论依据。
