[Effects of Ionizing Radiation on Intestinal Bile Acid Metabolism: Mechanism of the Radioprotective Effect of Glycoursodeoxycholic Acid].

Q3 Medicine 四川大学学报(医学版) Pub Date : 2024-09-20 DOI:10.12182/20240960403
Jun Dai, Yi Gao, Jian Wang, Shuyu Zhang, Pengfei Liu
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引用次数: 0

Abstract

Objective: Radioactive intestinal injury is a common complication during radiotherapy of tumors. The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells.

Methods: A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile acids were quantified using metabolomics analysis. IEC-6 cells, a small intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid (GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow cytometry. The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media. The expression levels of proteins associated with cell death were determined using Western blot.

Results: After exposure to irradiation, the small intestine tissues of the rats showed typical radioactive intestinal injury. In addition, various bile acids showed fluctuation before and after irradiation. Among the bile acids, GUDCA increased significantly at 3 d after irradiation, but returned to the pre-irradiation level at 7 d after irradiation. Compared with the control group, after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after irradiation was significantly higher than that of the DMSO group (P<0.05); the expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, were significantly lower than those in the control group (P<0.05). After GUDCA treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group (P<0.05). Compared with the DMSO control group, the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 6 Gy (P<0.05). D0, or the mean lethal dose, of the GUDCA group was 6.374, while that of the DMSO group was 4.572. Compared with the DMSO control group, the D0 value of the GUDCA treatment group increased, and the sensitization enhancement ratio (SER) was 0.717.

Conclusion: After exposing the abdomen of rats to irradiation, the intestinal bile acid metabolism of the rats will change significantly, and GUDCA can produce radioprotective effects on intestinal cells to a certain extent.

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[电离辐射对肠道胆汁酸代谢的影响:甘草去氧胆酸的辐射防护作用机制]。
目的:放射性肠道损伤是肿瘤放疗过程中常见的并发症。本研究旨在观察电离辐射对肠道胆汁酸短期变化的影响,并探讨胆汁酸对肠细胞的放射保护作用:方法:将大鼠腹部置于每天 2 Gy 的辐照下,连续照射 4 天,建立大鼠小肠损伤模型。采用代谢组学分析方法对胆汁酸进行定量分析。将小肠上皮细胞系 IEC-6 细胞分为接受二甲基亚砜(DMSO)和 0 Gy 照射的对照组、接受 GUDCA 和 0 Gy 照射的甘油去氧胆酸(GUDCA)实验组、接受 DMSO 和 10 Gy 照射的 DMSO 照射组和接受 GUDCA 和 10 Gy 照射的 GUDCA 照射组。细胞活力和细胞毒性通过 CCK-8 检测试验进行评估。细胞凋亡率通过流式细胞仪测定。细胞的集落形成率和辐射敏感性由固体培养基上的集落形成试验确定。用 Western 印迹法测定与细胞死亡相关的蛋白质的表达水平:结果:照射后,大鼠的小肠组织出现了典型的放射性肠损伤。此外,各种胆汁酸在辐照前后出现波动。在胆汁酸中,GUDCA 在辐照后 3 d 显著增加,但在辐照后 7 d 恢复到辐照前的水平。与对照组相比,20 μmol/L 的 GUDCA 处理 24 h 后,照射后的细胞存活率明显高于二甲基亚砜组(GUDCA 组的 PPPP0,即平均致死剂量为 6.374,而二甲基亚砜组为 4.572)。与 DMSO 对照组相比,GUDCA 治疗组的 D0 值增加,敏化增强比(SER)为 0.717:大鼠腹部接受辐照后,肠道胆汁酸代谢会发生显著变化,GUDCA能在一定程度上对肠道细胞产生辐射保护作用。
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来源期刊
四川大学学报(医学版)
四川大学学报(医学版) Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
0.70
自引率
0.00%
发文量
8695
期刊介绍: "Journal of Sichuan University (Medical Edition)" is a comprehensive medical academic journal sponsored by Sichuan University, a higher education institution directly under the Ministry of Education of the People's Republic of China. It was founded in 1959 and was originally named "Journal of Sichuan Medical College". In 1986, it was renamed "Journal of West China University of Medical Sciences". In 2003, it was renamed "Journal of Sichuan University (Medical Edition)" (bimonthly). "Journal of Sichuan University (Medical Edition)" is a Chinese core journal and a Chinese authoritative academic journal (RCCSE). It is included in the retrieval systems such as China Science and Technology Papers and Citation Database (CSTPCD), China Science Citation Database (CSCD) (core version), Peking University Library's "Overview of Chinese Core Journals", the U.S. "Index Medica" (IM/Medline), the U.S. "PubMed Central" (PMC), the U.S. "Biological Abstracts" (BA), the U.S. "Chemical Abstracts" (CA), the U.S. EBSCO, the Netherlands "Abstracts and Citation Database" (Scopus), the Japan Science and Technology Agency Database (JST), the Russian "Abstract Magazine", the Chinese Biomedical Literature CD-ROM Database (CBMdisc), the Chinese Biomedical Periodical Literature Database (CMCC), the China Academic Journal Network Full-text Database (CNKI), the Chinese Academic Journal (CD-ROM Edition), and the Wanfang Data-Digital Journal Group.
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