通过抑制 cGAS/STING 激活,饮食限制和禁食可减轻辐射诱导的肠道损伤。

IF 4.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Nutritional Biochemistry Pub Date : 2024-07-23 DOI:10.1016/j.jnutbio.2024.109707
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引用次数: 0

摘要

背景:肠道放射损伤是腹腔或盆腔放疗患者最常见的并发症之一,限制了这种治疗方法的临床应用。有证据表明,饮食限制对改善代谢状况和老年相关疾病有潜在益处。本研究探讨了饮食限制对辐射诱导的肠道损伤的影响和机制:方法:将小鼠随机分为对照组、10 Gy 全腹部照射(TAI)组、30% 热量限制(CR)预处理 7 天组或 TAI 前禁食 24 小时组。照射后,小鼠恢复自由饮食。辐射3.5天后,小鼠被处死,并采集组织样本:结果:CR和禁食通过恢复缩短的结肠长度、改善受损的肠道结构和渗透性以及重塑肠道微生物结构,减少了辐射引起的肠道损伤,促进了肠道恢复。CR 和禁食还能明显减少线粒体损伤和 DNA 损伤,进而减少环 GMP-AMP 合成酶/干扰素基因刺激器(cGAS/STING)通路的激活以及空肠中 I 型干扰素和其他趋化因子的产生。由于 cGAS/STING 通路与先天性免疫有关,我们进一步发现 CR 和禁食诱导空肠向免疫抑制性 M2 巨噬细胞极化,减少 CD8+ 细胞毒性 T 淋巴细胞,并下调空肠中的促炎因子:我们的研究结果表明,通过减少 cGAS/STING 介导的有害免疫反应,CR 和禁食可减轻辐射诱导的肠道损伤。
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Dietary restriction and fasting alleviate radiation-induced intestinal injury by inhibiting cGAS/STING activation

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24 h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8+ cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses.

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来源期刊
Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry 医学-生化与分子生物学
CiteScore
9.50
自引率
3.60%
发文量
237
审稿时长
68 days
期刊介绍: Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.
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