Inhibition of DDX3X alleviates persistent inflammation, immune suppression and catabolism syndrome in a septic mice model
Inhibition of DDX3X alleviates persistent inflammation, immune suppression and catabolism syndrome in a septic mice model
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DOI：
10.1016/j.intimp.2023.109779
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发表时间：
2023-02-18
影响因子：
5.6
通讯作者：
Wang，Yuchang
中科院分区：
文献类型：
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作者：
Liu，Yukun;Zhang，Yongsheng;Wang，Yuchang
DDX 3X参与多种病理过程，如感染、免疫和细胞死亡。本研究旨在探讨DDX 3X特异性抑制剂RK-33对脓毒症发展为持续性炎症、免疫抑制和卡介综合征（PICS）的影响。将小鼠随机分为4组：假手术组、假手术+ RK-33组（20 mg/kg，腹腔注射，1次/d）、CLP组和CLP + RK-33组（20 mg/kg，腹腔注射，1次/d）。计算外周血、脾脏和骨髓中的炎性细胞数量，并使用酶联免疫吸附试验检测炎性细胞因子。测量脓毒症小鼠的体重和骨骼肌质量，并使用伊红染色检查骨骼肌组织。Western blotting检测脓毒症小鼠骨骼肌中MuRF 1、atrogin 1和NLRP 3的表达水平。此外，活性氧化物种，超氧化物歧化酶和丙二醛进行了测量，使用商业kitch.ResultsRK-33减少炎症细胞计数和细胞因子水平在CLP小鼠，改善了CD 4和CD 8 T细胞的下降，并防止体重和骨骼肌质量的损失在脓毒症小鼠。此外，RX-33减少氧化应激在败血症小鼠的骨骼肌。ConclusionIn建立脓毒症小鼠模型，RK-33减轻炎症和氧化应激，改善CLP诱导的免疫抑制和骨骼肌萎缩，提高生存。这些发现表明，RK-33可能是一种新的潜在的治疗药物，用于预防脓毒症进展为PICS。
ObjectiveDDX3X is involved in various pathological processes such as infection, immunity and cell death. This study aimed to investigate the effect of RK-33, a specific inhibitor of DDX3X, on the progression of sepsis to persistent inflammation, immune suppression and catabolism syndrome(PICS).MethodsThe septic mice model was established using caecal ligation and perforation (CLP). The mice were randomly divided into four groups: sham group, sham + RK-33 group (20 mg/kg, intraperitoneal injection, once a day), CLP group and CLP + RK-33 group (20 mg/kg, intraperitoneal injection, once a day). The number of inflammatory cells in the peripheral blood, spleen and bone marrow was calculated, and inflammatory cytokines were detected using an enzyme-linked immunosorbent assay. The septic mice’s body weight and skeletal muscle mass were measured, and skeletal muscle tissues were examined using eosin staining. Western blotting was performed to detect the expression levels of MuRF1, atrogin1 and NLRP3 in the skeletal muscle of septic mice. Additionally, reactive oxidative species, superoxide dismutase and malondialdehyde were measured using commercial kits.ResultsRK-33 reduced inflammatory cell counts and cytokine levels in CLP mice, ameliorated the decline in CD4 and CD8 T cells and prevented the loss of body weight and skeletal muscle mass in septic mice. Additionally, RX-33 reduced oxidative stress in the skeletal muscle of septic mice.ConclusionIn the established sepsis mouse model, RK-33 alleviated inflammation and oxidative stress, ameliorated CLP-induced immunosuppression and skeletal muscle atrophy and improved survival. These findings suggest that RK-33 could be a novel potential therapeutic agent for preventing the progression of sepsis to PICS.