Danshensu methyl ester attenuated LPS-induced acute lung injury by inhibiting TLR4/NF-κB pathway

IF 1.9 4区 医学 Q3 PHYSIOLOGY
Xuejia Han , Wensi Ding , Guiwu Qu , Youjie Li , Pingyu Wang , Jiahui Yu , Mingyue Liu , Xiulan Chen , Shuyang Xie , Jiankai Feng , Sen Xu
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Abstract

Acute Lung Injury (ALI) manifests as an acute exacerbation of pulmonary inflammation with high mortality. The potential application of Danshensu methyl ester (DME, synthesized in our lab) in ameliorating ALI has not been elucidated. Our results demonstrated that DME led to a remarkable reduction in lung injury. DME promoted a marked increase in antioxidant enzymes, like superoxide dismutase (SOD), and glutathione (GSH), accompanied by a substantial decrease in reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA). Moreover, DME decreased the production of IL-1β, TNF-α and IL-6, in vitro and in vivo. TLR4 and MyD88 expression is reduced in the DME-treated cells or tissues, which further leading to a decrease of p-p65 and p-IκBα. Meanwhile, DME effectively facilitated an elevation in cytoplasmic p65 expression. In summary, DME could ameliorate ALI by its antioxidant functionality and anti-inflammation effects through TLR4/NF-κB, which implied that DME may be a viable medicine for lung injury.

Abstract Image

丹参素甲酯通过抑制 TLR4/NF-κB 通路减轻 LPS 诱导的急性肺损伤
急性肺损伤(ALI)表现为肺部炎症的急性加重,死亡率很高。丹参素甲酯(DME,由我们实验室合成)在改善急性肺损伤方面的潜在应用尚未阐明。我们的研究结果表明,丹参素甲酯能显著减轻肺损伤。DME促进了超氧化物歧化酶(SOD)和谷胱甘肽(GSH)等抗氧化酶的明显增加,同时大幅减少了活性氧(ROS)、髓过氧化物酶(MPO)和丙二醛(MDA)。此外,DME 还能减少体外和体内 IL-1β、TNF-α 和 IL-6 的产生。TLR4和MyD88在经DME处理的细胞或组织中的表达减少,从而进一步导致p-p65和p-IκBα的减少。同时,DME能有效促进细胞质p65表达的增加。综上所述,二甲双胍可通过其抗氧化功能和TLR4/NF-κB的抗炎作用改善ALI,这意味着二甲双胍可能是一种治疗肺损伤的可行药物。
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来源期刊
CiteScore
4.80
自引率
8.70%
发文量
104
审稿时长
54 days
期刊介绍: Respiratory Physiology & Neurobiology (RESPNB) publishes original articles and invited reviews concerning physiology and pathophysiology of respiration in its broadest sense. Although a special focus is on topics in neurobiology, high quality papers in respiratory molecular and cellular biology are also welcome, as are high-quality papers in traditional areas, such as: -Mechanics of breathing- Gas exchange and acid-base balance- Respiration at rest and exercise- Respiration in unusual conditions, like high or low pressure or changes of temperature, low ambient oxygen- Embryonic and adult respiration- Comparative respiratory physiology. Papers on clinical aspects, original methods, as well as theoretical papers are also considered as long as they foster the understanding of respiratory physiology and pathophysiology.
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