Abstract：
In patients with high-level radiation exposure, gastrointestinal injury is the main cause of death. Despite the severity of damage to the gastrointestinal tract, no specific therapeutic option is available. Tauroursodeoxycholic acid (TUDCA) is a conjugated form of ursodeoxycholic acid that suppresses endoplasmic reticulum (ER) stress and regulates various cell-signaling pathways. We investigated the effect of TUDCA premedication in alleviating intestinal damage and enhancing the survival of C57BL/6 mice administered a lethal dose (15Gy) of focal abdominal irradiation. TUDCA was administered to mice 1 h before radiation exposure, and reduced apoptosis of the jejunal crypts 12 h after irradiation. At later timepoint (3.5 days), irradiated mice manifested intestinal morphological changes that were detected via histological examination. TUDCA decreased the inflammatory cytokine levels and attenuated the decrease in serum citrulline levels after radiation exposure. Although radiation induced ER stress, TUDCA pretreatment decreased ER stress in the irradiated intestinal cells. The effect of TUDCA indicates the possibility of radiation therapy for cancer in tumor cells. TUDCA did not affect cell proliferation and apoptosis in the intestinal epithelium. TUDCA decreased the invasive ability of the CT26 metastatic colon cancer cell line. Reduced invasion after TUDCA treatment was associated with decreased matrix metalloproteinase (MMP)-7 and MMP-13 expression, which play important roles in invasion and metastasis. This study shows a potential role of TUDCA in protecting against radiation-induced intestinal damage and inhibiting tumor cell migration without any radiation and radiation therapy effect.
摘要：
在高水平辐射暴露的患者中，胃肠道损伤是导致死亡的主要原因。尽管胃肠道损伤严重，没有具体的治疗选择。牛磺熊去氧胆酸(TUDCA)是熊去氧胆酸的缀合形式,其抑制内质网(ER)应激并调节各种细胞信号传导途径。我们研究了TUDCA前用药在减轻肠道损伤和提高C57BL/6小鼠的存活中的作用，这些小鼠施用了致死剂量（15Gy）的局灶性腹部照射。在辐射暴露前1小时对小鼠施用TUDCA，照射后12小时空肠隐窝的凋亡减少。在稍后的时间点（3.5天），辐照小鼠表现出肠道形态学变化，通过组织学检查检测到。辐射暴露后，TUDCA降低了炎性细胞因子水平，并减弱了血清瓜氨酸水平的降低。虽然辐射引起的内质网应激，TUDCA预处理降低了辐照肠细胞中的ER应激。TUDCA的作用表明肿瘤细胞中癌症的放射治疗的可能性。TUDCA不影响肠上皮细胞的增殖和凋亡。TUDCA降低了CT26转移性结肠癌细胞系的侵袭能力。TUDCA治疗后侵袭性降低与基质金属蛋白酶（MMP）-7和MMP-13表达降低有关，在侵袭和转移中起重要作用。这项研究显示了TUDCA在防止辐射诱导的肠道损伤和抑制肿瘤细胞迁移方面的潜在作用，而没有任何辐射和放射治疗作用。
