Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
Mol Biol Rep. 2023 Oct;50(10):8459-8467. doi: 10.1007/s11033-023-08762-1. Epub 2023 Aug 26.
Intestinal injury is one of the main side-effects of cisplatin chemotherapy, impairing the quality of life in patients with cancer. In this study, we investigated the protective effects of recombinant soluble thrombomodulin (rsTM), which is a potent anti-inflammatory agent, on cisplatin-induced intestinal injury.
We first evaluated the effects of rsTM on intestinal injury caused by cisplatin in mice in vivo. Disease progression was monitored by analyzing loss of body weight and histological changes in intestinal tissue. We then investigated the effects of rsTM on mouse intestinal organoid formation and growth in vitro. Gene expression levels were analyzed by quantitative real-time polymerase chain reaction and Western blotting.
rsTM treatment significantly attenuated the loss of body weight, histological damage and gene expression levels of pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α and high-mobility group box-1 in a cisplatin-treated mouse model. Furthermore, rsTM alleviated the inflammatory response and apoptosis in a cisplatin-treated intestinal epithelial organoid model.
rsTM suppresses cisplatin-induced intestinal epithelial cell-derived cytokine production and alleviates intestinal mucositis.
肠损伤是顺铂化疗的主要副作用之一，会损害癌症患者的生活质量。在这项研究中，我们研究了重组可溶性血栓调节蛋白（rsTM）对顺铂诱导的肠损伤的保护作用。
我们首先评估了 rsTM 对体内顺铂诱导的肠损伤的作用。通过分析体重减轻和肠道组织的组织学变化来监测疾病进展。然后，我们研究了 rsTM 对体外小鼠肠道类器官形成和生长的影响。通过定量实时聚合酶链反应和 Western blot 分析基因表达水平。
rsTM 治疗显著减轻了顺铂处理小鼠模型中体重减轻、组织学损伤和促炎细胞因子（如白细胞介素 6、肿瘤坏死因子-α和高迁移率族蛋白 1）的基因表达水平。此外，rsTM 减轻了顺铂处理的肠道上皮类器官模型中的炎症反应和细胞凋亡。
rsTM 抑制顺铂诱导的肠上皮细胞来源的细胞因子产生，并缓解肠道黏膜炎。
