冠心病人源肠道菌群小鼠模型 z-bo 2020-12-30 326

　　Objective: To establish a mouse model of intestinal flora from patients with coronary heart disease by fecal bacteria transplantation and evaluate the model. Methods: 28 sterile female C57BL/6J mice were divided into control (CON) group and model (CAD) group. Healthy volunteers and coronary heart disease patients were inoculated with fresh fecal suspensions, and each group was well-balanced 6 weeks and 10 weeks after transplantation. In 7 animals, feces, blood and aorta were collected for 16SrDNA, blood lipids, cytokines and histopathological examination.

　　Result: From the 5th week, the body weight of CAD group animals increased faster (P<0.05). α-diversity analysis, the Simpson index of the CAD group increased at two time points (P<0.05, P<0.01), Shannon index (P<0.05, P<0.01), ACE (P<0.05) and Chao1 index all decreased (P<0.05). CON group reads are mainly distributed in Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Fusobacteria, Actinobacteria , Cyanobacteria (Cyanobacteria), soft wall bacteria (Tenericutes). At 6 weeks of modeling, the abundance of Firmicutes and Soft-walled bacteria in the CAD group decreased (P<0.05), and the abundances of Bacteroides and Verrucomicrobia increased (P<0.01); at 10 weeks of modeling, The abundance of Firmicutes in the CAD group decreased (P<0.01), and the abundance of Bacteroides and Verrucomicrobia increased (P<0.01). β-diversity analysis showed that the intestinal types of CAD group and CON group were distributed in different areas, and the different stages of the same group were distributed in the same area. There were significant differences in the composition of microbial species between the CAD group and the CON group (P<0.05). In the CAD group, blood triglycerides (TG) (P<0.05, P<0.01), cholesterol (TC) (P<0.05), lactate dehydrogenase (LDH) (P <0.0 P<0.0001) and phosphokinase (CK) (P<0.0 P<0.05) values both increased. Low-density lipoprotein (LDL-C) increased at 6 weeks of modeling (P<0.05). Cytokine detection, IL-6 concentration increased at 6 weeks of modeling (P<0.05), and decreased at 10 weeks (P<0.00001); IL-10 concentration decreased at 10 weeks of modeling (P<0.05); IL -2, IL-4, IL-5, IL1β increased in concentration at 10 weeks of modeling (P<0.000 P<0.05, P<0.000 P<0.01). There was no significant difference in IL-12p70, TNF-α, INF-γ at the two time points. The coronary artery hematoxylin-eosin (H.E) staining of the CAD group and the CON group showed no atherosclerotic changes such as foam cell formation at two time points after modeling.

　　 Conclusion: In this study, fecal bacteria transplantation was used to obtain coronary heart patient-derived microbiota mice. The structural abundance of intestinal microbiota, body weight, blood lipids, cytokine content and other indicators showed similar changes to the clinic.