亚慢性低砷暴露对大鼠肠道及菌群的影响研究
Effects of Subchronic Low-arsenic Exposure on Intestine and Gut Microbiota in Rats
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摘要: 通过构建低剂量亚砷酸钠中毒SD大鼠模型，初步探究低砷暴露对肠道损伤及菌群的影响。雄性SD大鼠随机分为NC组（正常组）、AS1组（砷染毒12周）、AS2组（砷染毒16周）给予亚砷酸钠1 mg·kg-1灌胃染毒，一周6 d，每天一次，实验终期收集各组大鼠血液和脏器。苏木精-伊红（HE）染色观察结肠组织病理学变化；16S rRNA基因检测技术检测肠道菌群的变化；显色基质鲎试剂盒检测肝门静脉中内毒素（LPS）水平。结果表明，砷组中结肠的肠绒毛排列紊乱，间隙大，随着砷暴露时间的增加，有炎性细胞的浸润，结肠的长度缩短，肠砷含量逐渐升高，肝门静脉中的LPS水平显著升高（P<0.05）。砷暴露后与正常组相比，厚壁菌门（Firmicutes）的丰度显著降低（P<0.05），拟杆菌门（Bacteroidota）的丰度增加；从属水平看在砷暴露组中保护性细菌的丰度减少，如Roseburia、Anaerovoracaceae和Blautia等，增加Faecalibaculum、丹毒丝菌（Erysipelotrichaceae）和Quinella（P<0.05）等条件致病菌的丰度，并且呈现时间依赖性增高。因此，亚慢性低剂量亚砷酸钠诱导大鼠肠道发生损伤，肠道菌群的组成结构发生改变。Abstract: The study aims to investigate the effects of subchronic arsenic exposure of low dose on intestinal injury and gut microflora by constructing sodium arsenite poisoning of low dose models on SD rat preliminarily. The male rats were randomly divided into three groups:NC group (normal feeding control group), AS1 group (arsenic-exposed for 12 weeks), AS2 group (arsenic-exposed for 16 weeks), the AS1 and AS2 group was gavage-administered with sodium arsenite at a dose of 1 mg·kg-1, once a day, 6 days a week, and blood and organs were collected. Histopathological changes of the rats colon tissue were examined by HE staining. The content of lipopolysaccharide (LPS) were measured by endotoxin kit in hepatic portal vein. The caecal microbiomes patterns were analysed using 16S rRNA amplicon sequencing. Our results showed that the arrangement of intestinal villus was disordered in the arsenic group, with increase in the arsenic-exposure time, and there were infiltration of inflammatory cells in colon tissue. Meanwhile, compared with control group, the length of the colon was significantly shortened in arsenic group (P<0.05). The arsenic content of colon and the LPS contents were significantly increased compared with the control group (P<0.05). Besides, arsenic-exposure could significantly decrease the abundance of Firmicutes and increase the abundance of Bacteroidota (P<0.05). In the level of genus, compared with the normal group, arsenic-exposure reduced the abundance of protective bacteria, such as Roseburia, Anaerovoracaceae, Blautia, and increased the abundance of opportunistic pathogens, such as Faecalibaculum, Erysipelotrichac, Quinella (P<0.05), and showed a time-dependent increasing trend. Therefore, subchronic low-arsenic exposure could induce intestinal damage in rats, and the composition and structure of the intestinal microbiota were changed.
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Key words:
- sodium arsenite /
- SD rats /
- intestinal microbiota /
- colon /
- inflammation
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