动物造模,阿尔茨海默症 z-bio 2021-07-28 284

　　Objective: To use fecal bacterial transplantation to obtain human intestinal flora of Alzheimer's disease model mice through oral route, and to evaluate the model through bioinformatics and histopathology methods.

　　Method: 28 infertile female C57BL/6J mice were randomly divided into Alzheimer's disease model (AD) group and control group (CON) group, and Alzheimer's disease patients and healthy volunteers were respectively inoculated by oral route. 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 compared with CON is important. 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 the formation of senile plaques, the level of L-1β decreased at 6 weeks after modeling (Pu003c0.05), and IL-10 increased at 6 weeks after modeling (Pu003c0.01); TGF-β was created at 10 hours The concentration of the mold perimeter was 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.