Zhao Zhe, He Dan, Wang Jinyu, Xiao Yu, Gong Lixin, Tang Can, Peng Haibo, Qiu Xuemei, Liu Rui, Zhang Tao, Li Jingyi
The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China.
School of Laboratory Medicine, Chengdu Medical College, Chengdu, China.
Mol Cell Biochem. 2025 Apr;480(4):2277-2290. doi: 10.1007/s11010-024-05030-z. Epub 2024 May 25.
Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.
放射治疗是盆腔腹部肿瘤的传统治疗方法。然而,它会对小肠和结肠直肠造成一些损伤,这些部位对辐射非常敏感。辐射诱导的肠道损伤(RIII)会影响放射治疗的预后,导致功能丧失的后遗症,并对患者的生活质量造成长期损害。獐牙菜苦苷是一种糖苷,据报道它可以预防多种疾病,包括但不限于糖尿病、高血压、动脉粥样硬化、关节炎、疟疾和胃溃疡。然而,其对RIII的治疗效果和作用机制尚未明确。我们研究了獐牙菜苦苷是否对RIII具有保护作用。在本文中,我们使用辐照器建立辐射损伤的细胞和小鼠模型。预防性给予獐牙菜苦苷可以降低活性氧(ROS)和超氧阴离子水平,减轻辐射引起的细胞损伤。獐牙菜苦苷还减轻了小鼠的RIII,表现为更长的生存期、更少的体重减轻和更完整的肠道屏障。我们还发现,受辐射小鼠中初级胆汁酸的相对丰度增加,法尼醇X受体(FXR)激动剂和獐牙菜苦苷均可降低其水平,并且通过环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白(cGAS-STING)途径减少下游干扰素和炎症因子,从而减轻辐射诱导的损伤。