动物造模,冠心病人源肠道菌群 z-bio 2022-09-13 283

　　Objective: To establish a mouse model of coronary heart disease-derived intestinal flora by fecal bacteria transplantation and evaluate the model.

　　METHODS: Twenty-eight sterile female C57BL/6J mice were divided into control (CON) group and model (CAD) group, respectively inoculated with fresh fecal suspension of healthy volunteers and patients with coronary heart disease, and each group was comforted at 6 and 10 weeks after transplantation. From 7 animals, feces, blood and aorta were collected for 16SrDNA, blood lipids, cytokines and histopathological examination.

　　RESULTS: From the 5th week, the body weight of the CAD group increased rapidly (P<0.05). α-diversity analysis, the Simpson index of CAD group increased at both time points (P<0.05, P<0.01), Shannon index (P<0.05, P<0.01), ACE (P<0.05) and Chao1 index decreased (P<0.05). The CON group reads are mainly distributed in Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Fusobacteria, Actinobacteria , Cyanobacteria, Tenericutes. At 6 weeks after modeling, the abundance of Firmicutes and Soft walled bacteria decreased in CAD group (P<0.05), while the abundances of Bacteroidetes and Verrucobacterium increased (P<0.01). The abundance of Firmicutes decreased in CAD group (P<0.01), while the abundance of Bacteroidetes and Verrucobacterium increased (P<0.01). β-diversity analysis showed that the intestinal types of CAD group and CON group were distributed in different regions, and different stages of the same group were distributed in the same region. There was a significant difference in microbial species composition between CAD group and CON group (P<0.05). Blood triglyceride (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 were increased. Low-density lipoprotein (LDL-C) was elevated at 6 weeks of modeling (P<0.05). Cytokine detection, the concentration of IL-6 increased at 6 weeks of modeling (P<0.05), and decreased at 10 weeks (P<0.00001); the concentration of IL-10 decreased at 10 weeks of modeling (P<0.05); -2, IL-4, IL-5, IL1β concentration increased at 10 weeks after 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 between the two time points. The coronary hematoxylin-eosin (H.E) staining of CAD group and CON group showed no atherosclerotic changes such as foam cell formation at two time points after modeling.

　　CONCLUSION: In this study, mice with coronary heart disease-derived microflora were obtained by fecal bacterial transplantation, and the intestinal microflora structure abundance, body weight, blood lipid, cytokine content and other indicators showed similar changes as in clinical practice.