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