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红花三味成分减轻脂多糖诱导的急性肺损伤并抑制 NET 释放。

Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide.

机构信息

Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai 200433, China.

出版信息

Mediators Inflamm. 2020 Feb 29;2020:2720369. doi: 10.1155/2020/2720369. eCollection 2020.

DOI:10.1155/2020/2720369
PMID:32189992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7066412/
Abstract

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.

摘要

血必净注射液是一种中国草药复合物,用于治疗中国的脓毒症,但它含有许多不同种类的成分,每种成分在治疗脓毒症方面可能具有不同的作用。本研究旨在探讨血必净的三种成分,红花黄色素 A(SYA)、羟基红花黄色素 A(HSYA)和脱水红花黄色素 B(AHSYB),在脂多糖(LPS)诱导的急性肺损伤(ALI)中的作用。通过气管内注射 LPS(10mg/kg)诱导小鼠急性肺损伤,然后用 SYA、HSYA 和 AHSYB 进行治疗。采集血液、支气管肺泡灌洗液(BALF)和肺组织,以检测肺损伤程度、炎症水平和中性粒细胞胞外陷阱(NETs)。使用佛波醇肉豆蔻酸酯(PMA)刺激 HL-60 细胞进行体外实验。SYA、HSYA 和 AHSYB 减轻了 LPS 诱导的肺损伤,组织病理学检测结果表明。这三种成分抑制 LPS 诱导的炎症因子和湿干重比升高,以及 BALF 中蛋白和细胞数量增加。它们还在免疫荧光检测中明显减少了髓过氧化物酶(MPO)和组蛋白的覆盖,并降低了血浆中 MPO-DNA 复合物的水平。体外实验表明,这三种成分抑制了 PMA 诱导的中性粒细胞样 HL-60 细胞中 NET 的释放。Western blot 表明,LPS 处理的小鼠肺组织和 PMA 处理的 HL-60 细胞中 c-快速加速纤维肉瘤(c-Raf)、丝裂原活化蛋白激酶 ERK 激酶(MEK)和细胞外信号调节激酶(ERK)的磷酸化均被 SYA、HSYA 和 AHSYB 显著降低。因此,我们的数据表明,XBJ 的三种成分,包括 SYA、HSYA 和 AHSYB,对 LPS 诱导的肺损伤和 NET 释放具有保护作用。

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