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芹菜素通过下调 TLR4/MyD88/NF-κB 信号通路缓解脂多糖诱导的急性肺损伤中的炎症反应。

Umbelliferone Alleviates Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury by Down-Regulating TLR4/MyD88/NF-κB Signaling.

机构信息

Iintensive Care Unit, Heze Municipal Hospital, No. 2888, West Caozhou Road, Heze, 274031, China.

出版信息

Inflammation. 2019 Apr;42(2):440-448. doi: 10.1007/s10753-018-00953-4.

DOI:10.1007/s10753-018-00953-4
PMID:30645708
Abstract

This study investigated the protective effect and underlying mechanism of action of umbelliferone (Umb) against lipopolysaccharide (LPS)-induced acute lung injury (ALI). An intragastric Umb injection prior to the administration of LPS dramatically decreased the wet/dry lung weight ratio, attenuated inflammatory cell infiltration in lung tissue, and reduced the LPS-induced production of inflammatory cytokines, including monocyte chemotactic protein-1(MCP-1), interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β, in broncheoalveolar lavage fluid (BALF). In addition, Umb resulted in significant anti-oxidative effects as shown by decreased myeloperoxidase (MPO) and malondialdehyde (MDA) activity and increased superoxide dismutase (SOD) activity compared with the LPS group. Finally, the inhibitory effects of Umb on the expression of toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway proteins were also measured. Our results clearly indicated that Umb exerted significant protective effects on LPS-induced ALI by inhibiting the activation of the TLR4/MyD88/NF-κB pathway.

摘要

本研究探讨了伞形酮(Umb)对脂多糖(LPS)诱导的急性肺损伤(ALI)的保护作用及其作用机制。LPS 给药前给予伞形酮腹腔注射可显著降低湿/干肺重比,减轻肺组织中炎性细胞浸润,并降低 LPS 诱导的炎症细胞因子产生,包括单核细胞趋化蛋白-1(MCP-1)、白细胞介素(IL)-6、肿瘤坏死因子-α(TNF-α)和 IL-1β,在支气管肺泡灌洗液(BALF)中。此外,与 LPS 组相比,伞形酮可显著抑制髓过氧化物酶(MPO)和丙二醛(MDA)活性,增加超氧化物歧化酶(SOD)活性,从而产生显著的抗氧化作用。最后,还测量了伞形酮对 toll 样受体 4(TLR4)/髓样分化蛋白 88(MyD88)/核因子-κB(NF-κB)信号通路蛋白表达的抑制作用。我们的研究结果清楚地表明,伞形酮通过抑制 TLR4/MyD88/NF-κB 通路的激活对 LPS 诱导的 ALI 发挥显著的保护作用。

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