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海藻糖对小鼠放射性肠损伤的防护作用及机制研究

Protective effect and mechanism of trehalose on ionizing radiation-induced intestinal damage in mice
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摘要 目的探讨海藻糖对小鼠放射性肠损伤的防护作用及分子机制。方法采用简单随机抽样法将8周龄的雄性C57 BL/6 J小鼠分为4组:对照组(不给予任何处理)、海藻糖组(饮用2 g/100 ml海藻糖水)、照射组(以13 Gy剂量对小鼠腹部照射)、海藻糖+照射组(饮用2 g/100 ml海藻糖水+以13 Gy剂量对小鼠腹部照射),每组6只。经13 Gy照射和2 g/100 ml海藻糖饮水处理后,每天记录小鼠体重,14 d后处死小鼠并采集小鼠的血液、小肠和结肠,测量结肠长度。采用苏木精-伊红(HE)染色法和过碘酸-雪夫(PAS)染色法评估小鼠肠道损伤程度;酶联免疫吸附实验(ELISA)检测血清和小肠组织中肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)的水平;小鼠小肠上皮MODE-K细胞增殖实验、细胞克隆形成实验、细胞凋亡检测实验、活性氧测定实验和DNA损伤检测实验分别检测细胞活力、细胞克隆形成能力、细胞凋亡率、活性氧水平和DNA双链断裂数量;实时定量聚合酶链式反应(qRT-PCR)法和Western blot法分别检测自噬相关基因mRNA和蛋白水平的表达情况。组间比较采用两独立样本t检验。结果动物实验结果显示,与照射组比较,海藻糖+照射组可显著缓解电离辐射(IR)后小鼠体重的下降,并可促进其恢复(t=4.064,P<0.05),且小鼠结肠缩短程度较轻,2组间的差异有统计学意义(t=4.044,P<0.05)。HE和PAS染色法评估结果显示,海藻糖可缓解IR后小鼠小肠黏膜损伤,与照射组比较,海藻糖+照射组小鼠绒毛较长、隐窝较深、杯状细胞数量较多,2组间的差异有统计学意义(t=4.373、8.414、6.515,均P<0.05)。ELISA检测结果显示,与照射组比较,海藻糖+照射组可显著降低IR后小鼠血清及小肠组织中TNF-α和IL-6的水平,且差异均有统计学意义(t=4.475、8.686、3.993、6.007,均P<0.05)。细胞增殖和克隆实验结果显示,与照射组比较,海藻糖+照射组可促进IR后小鼠小肠上皮MODE-K细胞活性和� Objective To investigate the protective effect and molecular mechanism of trehalose in ionizing radiation(IR)-induced small intestinal damage.Methods Eight-week-old male C57 BL/6 J mice were randomly divided into four groups,with each group containing six mice:control(no treatment given),trehalose-treated(consumption of 2 g/100 ml seaweed sugar water),IR(whole abdominal irradiation group treated with 13 Gy IR),and trehalose+IR groups(trehalose+total abdominal irradiation treatment with 13 Gy IR).Daily monitoring of body weight was performed after 13 Gy irradiation and 2 g/100 ml trehalose drinking water treatment.After 14 days,the mice were euthanized,and samples from the blood,small intestine,and colon were collected.Intestinal injury was assessed via hematoxylin-eosin(HE)and periodic acid-schiff(PAS)staining.The levels of tumor necrosis factor(TNF)-αand interleukin(IL)-6 in the serum and small intestine tissues were quantified through enzyme-linked immunosorbent assay(ELISA).Experiments on mouse small-intestine epithelial cell proliferation,cell clone formation,cell apoptosis rate,reactive oxygen species(ROS)determination,and DNA double-strand breaks(DSBs)detection were conducted to detect cell viability,clone formation ability,apoptosis,ROS levels,and the number of DSBs,respectively.The expression levels of autophagy-related genes and proteins were determined via quantitative real-time polymerase chain reaction(qRT-PCR)method and Western blot method.Inter group comparison was achieved through two independent sample t-tests.Results The animal study results demonstrated that compared with the irradiation group,trehalose significantly alleviated the weight loss,facilitated the recovery of irradiated mice,and promoted its recovery(t=4.064,P<0.05),the trehalose+IR group exhibited milder colon shortening degree of mice,and statistically significant difference(t=4.044,P<0.05).In addition,the HE and PAS staining evaluation results indicated that trehalose can alleviate intestinal mucosal damage in mice after IR.Compa
作者 江津 张松灵 赵舒雅 冯国兴 樊赛军 Jiang Jin;Zhang Songling;Zhao Shuya;Feng Guoxing;Fan Saijun(Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Sciences,Peking Union Medical College,Tianjin 300192,China)
出处 《国际放射医学核医学杂志》 2024年第4期244-256,共13页 International Journal of Radiation Medicine and Nuclear Medicine
基金 中国医学科学院医学与健康科技创新工程项目(No.2021-I2M-1-042)。
关键词 海藻糖 辐射 电离 辐射防护 辐射损伤 放射性肠炎 活性氧 自噬 Trehalose Radiation,ionizing Radiation Protection Radiation injuries Radiation enteritis Reactive oxygen species Autophagy
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