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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.

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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