动物造模,阿尔茨海默症 z-bio 2022-11-01 351

　　Objective To obtain a mouse model of human intestinal flora of Alzheimer's disease by oral fecal bacteria transplantation, and evaluate the model by bioinformatics, histopathology and other methods.

　　Methods Twenty eight sterile female C57BL/6J mice were randomly divided into the Alzheimer's disease model (AD) group and the control (CON) group. Fresh fecal suspension from patients with Alzheimer's disease and healthy volunteers was inoculated orally, respectively. After 6 and 10 weeks of transplantation, 7 animals in each group were euthanized, and the feces were taken for 16S rDNA detection; Brain tissue and blood were taken for AB content, cytokine detection, and brain tissue for histopathological examination.

　　Results There was no significant difference in body weight growth between CON group and AD group. α- Diversity analysis showed that Simpson index in AD group increased (P<0.05, P<0.01), ACE (P<0.05) and Chao1 (P<0.05), and Shannon index decreased (P<0.05, P<0.01) at two time points after modeling. There was significant difference compared with CON group. At the family level, the abundance of Bacteroides in AD group increased (P<0.01, P<0.05), while the abundance of Trichospirillaceae (P<0.001) and Digestive Streptococcaceae (P<0.01) decreased; At the genus level, the abundance of Bacteroides in AD group increased (P<0.01, P<0.05), the abundance of Clostridium (P<0.01, P<0.05), Trichospirillum (P<0.01, P<0.0001) and Parasitic bacteria (P<0.01, P<0.001) decreased, and there was a significant difference compared with CON. β- The results of diversity analysis showed that the intestinal types of AD group and CON group were distributed in the same region at different time points, and the intestinal types of different groups were distributed in different regions. The intestinal flora of the two groups of animals had significant difference in microbial species composition (P<0.05). A in blood and brain of AD mice at 10 weeks of modeling β The content of 40 increased (P<0.05, P<0.01), with a significant difference compared with CON group. Detection of cytokines related to senile plaque formation, L-1 β At the 6th week of modeling, the concentration decreased (P<0.05); IL-10 increased at 6 weeks of modeling (P<0.01); TGF- β At the 10th week of modeling, the concentration decreased (P<0.01), which was statistically significant compared with CON group. No senile plaque was found in histopathological examination.

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