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食品添加剂羧甲基纤维素钠通过破坏肠内环境加剧辐射对小鼠肠道的损伤

Food additive sodium carboxymethyl cellulose aggravates radiation-induced intestinal damage in mice by disrupting intestinal homeostasis
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摘要 目的 探究食品添加剂羧甲基纤维素钠(CMC-Na)的长期摄入对小鼠辐射耐受性的影响及其机制研究。方法 通过饲饮水中添加不同浓度CMC-Na(对照组,0.25%低剂量组,1%高剂量组)对小鼠进行饮食干预,而后建立辐射损伤模型(7 Gy, Co60γ射线)。在辐射干预前后,每周称量小鼠体质量变化,记录各组小鼠的死亡情况;干预8周后,检测血生化指标;ELISA、RT-qPCR和Western blot技术检测肠道相关细胞因子和蛋白变化情况;HE、免疫荧光及免疫组化染色切片观察肠道组织细胞形态的改变并进行病理评分;流式细胞术检测肠道干细胞比例。结果 通过流式细胞术检测发现,与对照组比较,两组饮食干预组的肠道干细胞比例均出现下降(P<0.05),下降程度与饮水中添加剂浓度呈正相关,且干细胞下降趋势在受到辐射损伤后持续存在。其中高剂量组死亡率显著升高(P<0.05),体质量大幅下降(P<0.000 1)。进一步实验发现肠道屏障功能受损,抑炎因子白介素-10(IL-10)含量下降。同时,高剂量组小鼠肠道中出现了TLR4、NF-κB、TNF-α以及IL-1β等炎症因子的高表达(P<0.05),并且在辐射损伤后进一步加剧;低剂量组小鼠部分炎症因子(NF-κB、TNF-α以及IL-1β)相较于对照组表达增高(P<0.05),但低于高剂量组。结论 长期摄入含有CMC-Na添加剂的饮食,会降低肠道内干细胞群的比例,加剧了辐射对肠道的损伤,降低了小鼠对辐射耐受性。 Objective To explore the effect and underlying mechanism of long-term intake of sodium carboxymethyl cellulose(CMC-Na),a food additive,on radiation tolerance in mice.Methods Dietary intervention was performed on the mice by adding different concentrations of CMC-Na to drinking water at a dose of 0,0.25%and 1%,respectively(Control and low-and high-dose groups)for 8 weeks,and then the mice were given a lethal radiation of 7 Gy 60 Co gamma rays to establish a radiation damage model.Before and after the radiation intervention,the body weight was measured weekly in every mice,and death was observed and recorded in each group.After an 8-week intervention,the blood biochemical indicators of mice were assessed.ELISA,Qrt-Pcr,and Western blotting techniques to investigate changes in intestinal-related cytokines and proteins.What’s more,HE staining,immunofluorescence assay and immunohistochemical staining were used to observe the changes of intestinal tissue morphology for pathological scores.Flow cytometry was employed to detect the proportion of intestinal stem cells.Results Flow cytometry showed that the proportion of intestinal stem cells was decreased in both dietary intervention groups when compared with the control group(P<0.05),and the decrease was positively correlated with the dose of CMC-Na in drinking water and persisted after radiation damage.Higher death rate(P<0.05)and obvious weight loss(P<0.0001)were observed in the high-dose intervention group,and impaired intestinal barrier function and a decrease in the content of the anti-inflammatory factor IL-10 were found in further research.Meanwhile,the expression levels of inflammatory factors such as TLR4,NF-κB,TNF-αand IL-1βwere higher in the high-dose intervention group(P<0.05),and the contents were further increased after radiation damage.The expression of certain inflammatory factors(NF-κB,TNF-α,and IL-1β)in the low-dose group exhibited a statistically significant increase compared to the control group(P<0.05),yet remained lower than that observed in
作者 刘绍庭 李忠俊 陈立 向阳 相丽欣 张薇薇 冉茜 王建 LIU Shaoting;LI Zhongjun;CHEN li;XIANG Yang;XIANG Lixin;ZHANG Weiwei;RAN Qian;WANG Jian(Department of Nutrition,Second Affiliated Hospital,Amy Medical University(Third Military Medical University),Chongqing,400037,China;Department of Blood Transfusion,Second Affiliated Hospital,Amy Medical University(Third Military Medical University),Chongqing,400037,China)
出处 《陆军军医大学学报》 CAS CSCD 北大核心 2024年第6期522-534,共13页 Journal of Army Medical University
基金 重庆市杰出青年基金(CSTC2021jcyj-jqx0004) 国家自然科学基金面上项目(81972973)。
关键词 羧甲基纤维素钠 辐射 肠道屏障 肠道干细胞 炎症 sodium carboxymethylcellulose radiation intestinal barrier intestinal stem cells inflammation
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