Résumé
Aim To explore the optimized tree shrews model of Alzheimer's disease through comparison of the pathology changes of brain neurons between the two kinds of tree shrew models.Methods Fifty tree shrews were randomly divided into five groups with 10 in each group:control group,high dose D-galactose combined with ibotenic acid (IBO) group,low dose D-galactose combined with IBO group [intraperitoneal injection D-galactose combined with IBO injection into bilateral basal nucleus of Meynert (BNM)],high dose Aβ25-35 combined with IBO group,and low dose Aβ25-35 combined with IBO group (injection into bilateral BNM).Hematoxylin and eosin (HE) staining was used to observe the morphological changes of brain neurons.The expressions of choline acetyltransterase (ChAT) and synaptophysin(SYP) in the brains were detected by immunohistochemical staining.Western blot was used to detect the expression of amyloid beta 1-42 (Aβ1-42),amyloid precursor protein (APP) and phosphorylated tau protein (p-tau).Results The HE staining showed there were different degrees of morphological changes in the brains of model groups.The changes in the high dose D-galactose and high dose Aβ25-35 combined with IBO group were more obvious than those in low dose D-galactose and Aβ25-35 combined with IBO group.Immunohistochemical staining revealed that the levels of ChAT and SYP in the model groups decreased compared with control group,and the decline in high dose Aβ25-35 combined with IBO group was more marked than that in low dose Aβ25-35 combined with IBO group(P ＜0.01).Western blot revealed that the levels of Aβ1-42,APP,p-tau in the model groups increased compared with control group,and the rise in high dose Aβ25-35 combined with IBO group was more apparent than that in low dose Aβ25-35 combined with IBO group (P ＜ 0.05 or P ＜ 0.01).Conclusion The method of modeling by Aβ25-35 combined with IBO injection into bilateral BNM is more suitable for the establishment of Alzheimer's disease model.