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红景天总苷通过抑制TLR4/NF-κB通路减轻脂多糖诱导的急性肺损伤。

Total glycosides of Rhodiola rosea L. attenuate LPS-induced acute lung injury by inhibiting TLR4/NF-κB pathway.

作者信息

Jia Xuehai, Zhang Ke, Feng Shushu, Li Yuyao, Yao Dahong, Liu Qiaohui, Liu Dong, Li Xin, Huang Jian, Wang Hangyu, Wang Jinhui

机构信息

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832002, China.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832002, China.

出版信息

Biomed Pharmacother. 2023 Feb;158:114186. doi: 10.1016/j.biopha.2022.114186. Epub 2022 Dec 30.

Abstract

Acute lung injury (ALI) is a common respiratory disease in clinics, which is characterized by alveolar-capillary membrane loss, plasma protein leakage, pulmonary edema, massive neutrophil infiltration, and the release of proinflammatory cytokines and mediators. Rhodiola rosea L. an adaptogenic plant rich in phenylethanoloids, phenylpropanoids, monoterpenes, has anti-inflammatory and antioxidant effects. We hope to verify the relieving effect of total glycosides of Rhodiola rosea L. (RTG) on ALI in mice and clarify its mechanism through this study. In this study, we identified the effect and mechanism of RTG on ALI through LPS-induced ALI mice. After RTG treatment, the pathological structure of lung tissue in ALI mice induced by LPS was significantly improved, and the infiltration of inflammatory cells was reduced. In addition, RTG reduced the production of IL-6, IL-1β, and TNF-α in the serum of ALI mice and reduced the content or activity of MPO, T-SOD, GSH, and MDA in lung tissue. RNAseq analysis showed that RTG ameliorated LPS-induced ALI through anti-inflammatory, reduced immune response, and anti-apoptotic activities. The western blotting analysis confirmed that RTG could down-regulate the expression levels of TLR4, MyD88, NF-κB p65, and p-IκBα/IκBα. These results suggest that RTG can attenuate LPS-induced ALI through antioxidants and inhibition of the TLR4/NF-κB pathway.

摘要

急性肺损伤(ALI)是临床上常见的呼吸系统疾病,其特征为肺泡-毛细血管膜损伤、血浆蛋白渗漏、肺水肿、大量中性粒细胞浸润以及促炎细胞因子和介质的释放。红景天是一种富含苯乙醇苷、苯丙烷类、单萜类的适应原植物,具有抗炎和抗氧化作用。我们希望通过本研究验证红景天总苷(RTG)对小鼠ALI的缓解作用并阐明其机制。在本研究中,我们通过脂多糖(LPS)诱导的ALI小鼠来确定RTG对ALI的作用及机制。RTG处理后,LPS诱导的ALI小鼠肺组织的病理结构明显改善,炎症细胞浸润减少。此外,RTG降低了ALI小鼠血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的产生,并降低了肺组织中髓过氧化物酶(MPO)、总超氧化物歧化酶(T-SOD)、谷胱甘肽(GSH)和丙二醛(MDA)的含量或活性。RNA测序分析表明,RTG通过抗炎、降低免疫反应和抗凋亡活性改善了LPS诱导的ALI。蛋白质免疫印迹分析证实,RTG可下调Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子κB p65(NF-κB p65)和磷酸化IκBα/ IκBα的表达水平。这些结果表明,RTG可通过抗氧化剂和抑制TLR4/NF-κB途径减轻LPS诱导的ALI。

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