动物造模,阿尔茨海默症,人源肠道菌群,动物模型 z-bio 2022-01-31 386

　　Objective: To adopt fecal bacterial transplantation to obtain human flora-related (HFA) model mouse Alzheimer's disease through oral route, and to evaluate the model through bioinformatics and histopathology methods.

　　Method: 28 sterile female C57BL/6J mice were randomly divided into Alzheimer's disease model (AD) group and control group (CON) group, and were orally vaccinated with Alzheimer's disease patients and healthy volunteers. The transplantation euthanized seven animals in each group. Stool was collected for 16SrDNA detection, brain tissue and blood were collected for AB content and cytokine detection, and brain tissue was collected for histopathological examination.

　　Result: There was no significant difference in animal weight gain between the CON group and the AD group. Alpha diversity analysis, AD group Simpson index increased (Pu003c0.05, Pu003c0.01), ACE (Pu003c0.05) and Chao1 (Pu003c0.05), after Shannon index modeling, both decreased scores (Pu003c0.05) 0.05, Pu003c0.01), the difference was significant compared with the CON group. At the family level, the abundance of Bacteroides in the AD group increased (Pu003c0.01, Pu003c0.05), and the abundance of Lacetospiraceae (Pu003c0.001) and Peptostreptococcaceae (Pu003c0.01) decreased. At the genus level, the abundance increased Bacteroides (Pu003c0.01, Pu003c0.05), Clostridia (Pu003c0.01, Pu003c0.05), Lacetospirillum (Pu003c ).01, Pu003c0.0001), and parasites (Pu003c0.01, Pu003c0) in the AD group .05)) Pu003c0.01, Pu003c0.001) decreased in abundance, and the difference is significant compared with CON. The results of β-diversity analysis showed that the intestinal types of the AD group and the CON group were distributed in the same area at different time points, and the intestinal types of different groups were distributed in different time intervals. There are significant differences in the composition of microbial species in the intestinal flora of the two groups of animals (Pu003c0.05). The blood and brain Aβ40 content of AD group increased after 10 weeks of modeling (Pu003c0.05, Pu003c0.01), which was significantly different from that of CON group. In the detection of cytokines related to senile plaque formation, the level of L-1β decreased at 6 weeks of modeling (Pu003c0.05), and IL-10 increased at 6 weeks of modeling (Pu003c0.01); TGF-β was 10 for modeling The weekly concentration decreased (Pu003c0.01), and the difference was statistically significant compared with the CON group. Histopathological examination revealed no formation of amyloid plaques.

　　Conclusion: In this study, we established a mouse model of human Alzheimer's disease flora by inoculating patient fecal suspension. The changes in the structural abundance of the intestinal flora of model mice and the cytokine content related to the formation of senile plaques are similar to the clinical manifestations of patients with Alzheimer's disease.