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替格瑞洛对内毒素血症的肺保护作用。

Lung protective effect of Ticagrelor in endotoxemia.

机构信息

Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Kufa, Iraq.

KMG Klinikum Güstrow, Clinic for Trauma Surgery, Spinal Surgery and Orthopedics, Güstrow, Germany.

出版信息

J Med Life. 2023 Jun;16(6):941-947. doi: 10.25122/jml-2022-0308.

DOI:10.25122/jml-2022-0308
PMID:37675176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10478651/
Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. This study aimed to investigate the potential protective effect of the lungs in sepsis by modulating inflammatory and oxidative stress markers. Twenty-four adult male Swiss-albino mice, aged 8-12 weeks and weighing 20-30 g, were divided into four equal groups (n=6): sham (laparotomy only), CLP (laparotomy plus cecal ligation and puncture), vehicle (DMSO administered one hour before CLP), and Ticagrelor (50 mg/kg IP administered one hour before CLP). Tissue levels of pro-inflammatory and oxidative stress markers in the lung were assessed using ELISA. F2 isoprostane levels were significantly higher in the sepsis group (p<0.05) compared to the sham group, while Ticagrelor significantly decreased the inflammatory and oxidative stress markers compared to the sepsis group. All mice in the sepsis group had considerable (p=0.05) lung tissue damage, but Ticagrelor considerably decreased lung tissue injury (p=0.05). Furthermore, Ticagrelor was found to reduce tissue cytokine levels of the lung (IL-1, TNF a, IL-6, F2 isoprostane, GPR 17, MIF) in male mice during CLP-induced polymicrobial sepsis by modulation of pro-inflammatory and oxidative stress cascade signaling pathways.

摘要

脓毒症是一种危及生命的器官功能障碍,由宿主对感染的失调反应引起。本研究旨在通过调节炎症和氧化应激标志物来研究肺部在脓毒症中的潜在保护作用。将 24 只成年雄性瑞士白化病小鼠(8-12 周龄,体重 20-30g)分为四组(n=6):假手术(仅剖腹术)、CLP(剖腹术加盲肠结扎和穿刺)、载体(CLP 前 1 小时给予 DMSO)和 Ticagrelor(CLP 前 1 小时给予 50mg/kg IP)。使用 ELISA 评估肺部促炎和氧化应激标志物的组织水平。与假手术组相比,脓毒症组 F2 异前列腺素水平显著升高(p<0.05),而 Ticagrelor 与脓毒症组相比,显著降低了炎症和氧化应激标志物。所有脓毒症组的小鼠均有相当程度的(p=0.05)肺组织损伤,但 Ticagrelor 显著降低了肺组织损伤(p=0.05)。此外,Ticagrelor 被发现通过调节促炎和氧化应激级联信号通路,降低 CLP 诱导的多微生物脓毒症雄性小鼠肺部组织细胞因子水平(IL-1、TNF-a、IL-6、F2 异前列腺素、GPR17、MIF)。

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Ticagrelor Protects against Sepsis-Induced Acute Kidney Injury through an Adenosine Receptor-Dependent Pathway.替格瑞洛通过腺苷受体依赖性途径预防脓毒症相关性急性肾损伤。
Curr Med Sci. 2022 Jun;42(3):505-512. doi: 10.1007/s11596-022-2516-5. Epub 2022 Jun 8.
3
Downregulation of macrophage migration inhibitory factor attenuates NLRP3 inflammasome mediated pyroptosis in sepsis-induced AKI.
巨噬细胞移动抑制因子的下调减轻脓毒症诱导的急性肾损伤中NLRP3炎性小体介导的细胞焦亡。
Cell Death Discov. 2022 Feb 14;8(1):61. doi: 10.1038/s41420-022-00859-z.
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Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients.在败血症小鼠模型中的转录反应反映了败血症患者的转录反应。
Int J Mol Sci. 2022 Jan 13;23(2):821. doi: 10.3390/ijms23020821.
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Assessment of Sumatriptan on Sepsis-Induced Kidney injury in the Cecal Ligation and Puncture Mice Model.评估舒马曲坦对盲肠结扎穿刺诱导的小鼠脓毒症肾损伤的作用。
Drug Res (Stuttg). 2022 Mar;72(3):156-162. doi: 10.1055/a-1685-0482. Epub 2021 Dec 1.
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