动物造模,冠心病人源肠道菌群小鼠模型 z-bio 2022-11-02 298

　　Objective: To establish a mouse model of human intestinal flora of coronary heart disease 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. They were inoculated with fresh fecal suspension from healthy volunteers and patients with coronary heart disease, respectively. At 6 and 10 weeks after transplantation, 7 animals in each group were euthanized. Feces, blood, and aorta were taken for 16S rDNA, blood lipids, cytokines, and histopathological examination.

　　Results: The weight of animals in CAD group increased rapidly from the fifth week (P<0.05). α- Diversity analysis showed that Simpson index in 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 decreased (P<0.05). reads in CON group were mainly distributed in Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Fusobacteria, Actinobacteria, Cyanobacteria and Tenericutes. At the 6th week of modeling, the abundance of Firmicutes and Softicutes in CAD group decreased (P<0.05), while the abundance of Bacteroides and Microbacter verrucosa increased (P<0.01); At the 10th week of modeling, the abundance of Firmicutes in CAD group decreased (P<0.01), while the abundance of Bacteroides and Microbacter verrucosa 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 significant difference in microbial species composition between CAD group and CON group (P<0.05). At 6 and 10 weeks of modeling, the values of triglyceride (TG) (P<0.05, P<0.01), cholesterol (TC) (P<0.05), lactate dehydrogenase (LDH) (P<0.0001) and phosphokinase (CK) (P<0.05) in blood of CAD group mice increased. Low density lipoprotein (LDL-C) increased at the 6th week of modeling (P<0.05). Cytokine detection showed that the concentration of IL-6 increased at 6 weeks (P<0.05) and decreased at 10 weeks (P<0.0001); The concentration of IL-10 decreased at the 10th week of modeling (P<0.05); IL-2、IL-4、IL-5、IL1 β At the 10th week of modeling, the concentration increased (P<0.000 P<0.05, P<0.000 P<0.01). IL-12p70、TNF- α、 INF- γ There was no significant difference between the two time points. The coronary artery hematoxylin eosin (H.E) staining of mice in CAD group and CON group showed no atherosclerosis changes such as foam cell formation at two time points after modeling.

　　Conclusion: In this study, fecal bacteria transplantation was used to obtain the flora of mice from patients with coronary heart disease, and the intestinal flora structure abundance, body weight, blood lipid, cytokine content and other indicators showed similar changes to those in clinical practice.