Background Ionizing radiation (IR)-induced intestinal injury is a major side effect and dose-limiting toxicity in patients receiving radiotherapy. There is an urgent need to identify an effective and safe radioprotectant to reduce radiation-induced intestinal injury. Immunoregulation is considered an effective strategy against IR-induced injury. The purpose of this article was to investigate the protective effect of Nocardia rubra cell wall skeleton (Nr-CWS), an immunomodulator, on radiation-induced intestinal damage and to explore its potential mechanism. Methods C57BL/6 J male mice exposed to 12 Gy whole abdominal irradiation (WAI) were examined for survival rate, morphology and function of the intestine and spleen, as well as the gut microbiota, to comprehensively evaluate the therapeutic effects of Nr-CWS on radiation-induced intestinal and splenetic injury. To further elucidate the underlying mechanisms of Nr-CWS-mediated intestinal protection, macrophages were depleted by clodronate liposomes to determine whether Nr-CWS-induced radioprotection is macrophage dependent, and the function of peritoneal macrophages stimulated by Nr-CWS was detected in vitro. Results Our data showed that Nr-CWS promoted the recovery of intestinal barrier function, enhanced leucine-rich repeat-containing G protein-coupled receptor 5+ intestinal stem cell survival and the regeneration of intestinal epithelial cells, maintained intestinal flora homeostasis, protected spleen morphology and function, and improved the outcome of mice exposed to 12 Gy WAI. Mechanistic studies indicated that Nr-CWS recruited macrophages to reduce WAI-induced intestinal damage. Moreover, macrophage depletion by clodronate liposomes blocked Nr-CWS-induced radioprotection. In vitro, we found that Nr-CWS activated the nuclear factor kappa-B signaling pathway and promoted the phagocytosis and migration ability of peritoneal macrophages. Conclusions Our study suggests the therapeutic effect of Nr-CWS on radiation-induced intestinal injury, and provides possible therapeutic strategy and potential preventive and therapeutic drugs to alleviate it.

中文翻译：

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红色诺卡氏菌细胞壁骨架通过调节巨噬细胞功能减轻全腹部辐照诱导的肠道损伤


背景 电离辐射（IR）引起的肠道损伤是接受放射治疗的患者的主要副作用和剂量限制性毒性。迫切需要找到一种有效且安全的辐射防护剂来减少辐射引起的肠道损伤。免疫调节被认为是对抗红外线引起的损伤的有效策略。本文旨在研究免疫调节剂红色诺卡氏菌细胞壁骨架（Nr-CWS）对辐射所致肠道损伤的保护作用并探讨其潜在机制。方法 对 C57BL/6 J 雄性小鼠进行 12 Gy 全腹部照射（WAI）后，检测其存活率、肠、脾形态和功能以及肠道菌群，综合评估 Nr-CWS 对小鼠的治疗效果。辐射引起的肠和脾损伤。为了进一步阐明Nr-CWS介导的肠道保护的潜在机制，通过氯膦酸盐脂质体消耗巨噬细胞以确定Nr-CWS诱导的辐射保护是否是巨噬细胞依赖性的，并在体外检测Nr-CWS刺激的腹膜巨噬细胞的功能。结果我们的数据显示，Nr-CWS促进肠道屏障功能的恢复，增强富含亮氨酸重复序列的G蛋白偶联受体5+肠道干细胞的存活和肠上皮细胞的再生，维持肠道菌群稳态，保护脾脏形态和功能，并改善了暴露于 12 Gy WAI 的小鼠的结果。机制研究表明，Nr-CWS 招募巨噬细胞来减少 WAI 引起的肠道损伤。此外，氯膦酸盐脂质体消耗巨噬细胞可阻断 Nr-CWS 诱导的辐射防护。 在体外，我们发现Nr-CWS激活核因子kappa-B信号通路，促进腹腔巨噬细胞的吞噬和迁移能力。结论本研究提示Nr-CWS对放射性肠道损伤具有治疗作用，并为缓解放射性肠道损伤提供可能的治疗策略和潜在的预防和治疗药物。