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表儿茶素调控 miR-182/GGPPS1 信号通路抑制脂多糖诱导的小鼠急性肺损伤。

Catechin regulates miR-182/GGPPS1 signaling pathway and inhibits LPS-induced acute lung injury in mice.

机构信息

Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, China.

Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nankai University, Tianjin, China.

出版信息

Immunopharmacol Immunotoxicol. 2022 Feb;44(1):58-66. doi: 10.1080/08923973.2021.2002890. Epub 2021 Nov 30.

Abstract

AIM

Acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS) are detrimental inflammatory disease associated with high rates of morbidity and mortality due to a lack of effective treatment options. Previous study has demonstrated that an inhibition of geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1) show a protective effect against ALI.

METHOD

In this study, by using connective map (CMAP), we identified catechin as a potential drug to exhibit similar effects to inhibit GGPPS1. Furthermore, we detected the protective effect of catechin on lipopolysaccharide (LPS)-induced ALI and delineated the underlying mechanism.

RESULTS

We found that catechin effectively ameliorated LPS-induced lung inflammation and alleviated the release of cytokines into alveolar space. Notably, miR-182/GGPPS1 signaling pathway was reactivated upon catechin administration, which was essential for the catechin-induced protective effect against ALI.

CONCLUSION

catechin regulates miR-182/GGPPS1 signaling pathway and efficaciously ameliorates LPS-induced acute lung injury in mice model, which provided a promising therapeutic strategy in ALI and ARDS.

摘要

目的

急性肺损伤(ALI)和由此导致的急性呼吸窘迫综合征(ARDS)是一种有害的炎症性疾病,由于缺乏有效的治疗选择,其发病率和死亡率都很高。先前的研究表明,抑制香叶基香叶基焦磷酸合酶大亚基 1(GGPPS1)对 ALI 具有保护作用。

方法

在这项研究中,我们使用连接映射(CMAP)技术,鉴定出表儿茶素是一种具有类似抑制 GGPPS1 作用的潜在药物。此外,我们还检测了表儿茶素对脂多糖(LPS)诱导的 ALI 的保护作用,并阐明了其潜在的机制。

结果

我们发现表儿茶素能有效改善 LPS 诱导的肺炎症,并减轻细胞因子向肺泡空间的释放。值得注意的是,表儿茶素给药后重新激活了 miR-182/GGPPS1 信号通路,这对于表儿茶素诱导的 ALI 保护作用至关重要。

结论

表儿茶素调节 miR-182/GGPPS1 信号通路,有效改善 LPS 诱导的小鼠急性肺损伤,为 ALI 和 ARDS 提供了一种有前途的治疗策略。

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