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大承气汤通过 TLR4/NF-κB 信号通路减轻内毒素诱导的急性肺损伤及其机制的研究。

Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF-κB signaling pathway in vivo and in vitro.

机构信息

Department of Emergency, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Physical & Environmental Sciences, University of Toronto, Toronto, Canada.

出版信息

J Cell Biochem. 2019 Jun;120(6):8956-8964. doi: 10.1002/jcb.27615. Epub 2019 Mar 6.

DOI:10.1002/jcb.27615
PMID:30838705
Abstract

BACKGROUND AND OBJECTIVES

Sepsis that arises from uncontrolled pulmonary inflammation could induce acute lung injury (ALI), leading to the high death rate. Dachengqi decoction (DCQD) is a common traditional Chinese herbal medicine with strong anti-inflammatory effects. The current study aimed to explore the effect of DCQD on the inflammatory cytokines production, the aquaporin-1 (AQP-1) and AQP-5 protein expression in lipopolysaccharide (LPS)-induced ALI models, and the potential mechanisms underlying its effects.

METHODS

Sprague-Dawley rats and HULEC-5a cells were used as study models in the research. To detect related molecules in the study, the real-time polymerase chain reaction analysis, cell counting kit-8 assay, Western blot analysis, and enzyme-linked immunosorbent assay were performed.

RESULTS

DCQD could inhibit the expression of LPS-induced inflammatory cytokines, including interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α), in lung tissues and could reduce pulmonary edema by upregulating the expression of AQP-1 and AQP-5 in rats with LPS-induced ALI. Moreover, the results suggested that the toll-like receptor 4 (TLR4)/NF-κB signaling is indispensable for DCQD to increase the expression of AQP-1 and AQP-5 and inhibits the production of IL-6, IL-8, and TNF-α in LPS-induced HULEC-5a cells.

CONCLUSION

The results of our study suggested that DCQD suppresses the TLR4/NF-κB signaling pathway, increases the protein expression of AQP-1 and AQP-5, and inhibits the production of inflammatory cytokines, by which it may alleviate the inflammatory reactions in ALI and benefit the treatments.

摘要

背景与目的

失控的肺部炎症引发的脓毒症可导致急性肺损伤(ALI),从而导致高死亡率。大承气汤(DCQD)是一种具有强大抗炎作用的常用中药。本研究旨在探讨 DCQD 对脂多糖(LPS)诱导的 ALI 模型中炎症细胞因子产生、水通道蛋白-1(AQP-1)和 AQP-5 蛋白表达的影响及其作用机制。

方法

本研究以 Sprague-Dawley 大鼠和 HULEC-5a 细胞为研究模型。采用实时聚合酶链反应分析、细胞计数试剂盒-8 检测、Western blot 分析和酶联免疫吸附试验检测相关分子。

结果

DCQD 可抑制 LPS 诱导的炎症细胞因子(包括白细胞介素-6(IL-6)、IL-8 和肿瘤坏死因子-α(TNF-α))在肺组织中的表达,并通过上调 LPS 诱导的 ALI 大鼠中 AQP-1 和 AQP-5 的表达来减轻肺水肿。此外,结果表明 TLR4/NF-κB 信号通路对 DCQD 增加 AQP-1 和 AQP-5 的表达以及抑制 LPS 诱导的 HULEC-5a 细胞中 IL-6、IL-8 和 TNF-α的产生是必不可少的。

结论

本研究结果表明,DCQD 通过抑制 TLR4/NF-κB 信号通路,增加 AQP-1 和 AQP-5 的蛋白表达,抑制炎症细胞因子的产生,从而减轻 ALI 的炎症反应,有益于治疗。

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