Abstract: Objective To explore the effects of Shenzhiling oral liquid ( SZL) on neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) interaction, and determine which downstream extracellular signal-regulated kinase ( ERK) / cAMP-response element binding protein ( CREB) signaling pathway regulates the learning and memory ability in a mouse model of sporadic Alzheimer’ s disease ( SAD). Methods Twelve of 72 C57BL/ 6J male mice were randomly selected as the control group. The remaining 60 mice had streptozotocin injected into the bilateral ventricles on the first and third days to create a model of SAD; the streptozotocin was replaced with an equal volume of artificial cerebrospinal fluid in the control group. The 60 SAD mice were randomly divided into the model group, donepezil group, high-dose SZL(SZL-H), medium-dose SZL(SZL-M) and low-dose SZL(SZL-L) groups. Each intervention group was gavaged with the corresponding drug for 3 months, whereas the control group and model group were gavaged with the same volume of 0. 5% sodium carboxymethyl cellulose. The Morris water maze was used to test the escape latency and number of times each mouse crossed the platform after being removed from the platform. The number of synapses in the hippocampal CA1 region in each group was observed by transmission electron microscopy. The interaction between nNOS and CAPON in the hippocampus was detected by co-immunoprecipitation. The distribution and presence of ERK and CREB cells in the hippocampal CA1 region were observed by immunohistochemical staining. Western blot analysis was used to detect the expressions of ERK, p-ERK, CREB and p-CREB in hippocampal tissue. Results Compared with the control group, the model group had significantly increased escape latency ( P< 0.01), decreased frequency of platform crossing (P< 0. 01), decreased number of synapses in the hippocampal CA1 region ( P< 0. 01), increased interaction between nNOS and CAPON (P<0.01), similar expression of ERK (P>0. 05), decreased expressions of p-ERK, CREB and p-CREB ( P< 0.01), and decreased concentrations of p-ERK/ ERK and p-CREB/ CREB ( P< 0. 01). Compared with the model group, the donepezil and SZL intervention groups had significantly decreased escape latency (P<0.05 or P<0.01), increased frequency of platform crossing (P<0.01), increased numbers of synapses in the hippocampal CA1 region (P<0. 01), decreased interaction between nNOS and CAPON (P<0.05 or P<0.01), similar expression of ERK ( P> 0.05), increased expressions of p-ERK, CREB and p-CREB ( P<0. 05 or P< 0.01), and increased concentrations of p-ERK/ ERK and p-CREB/ CREB (P<0.01). Conclusions SZL improves the learning and memory ability of mice with SAD by decreasing the interaction between nNOS and CAPON and increasing the expression of ERK/ CREB pathway-related proteins and the number of synapses.

Abstract: Objective To explore the effects of Jisheng Shenqi decoction on homing of bone marrow mesenchymal stem cells (BMSCs) based on the SDF-1/ CXCR4 axis and analyze the mechanism of liver cirrhosis treatment with Jisheng Shenqi decoction combined with BMSCs transplantation. Methods A liver cirrhosis model was established by intraperitoneal injection of 40% carbon tetrachloride oil solution and other complex factors in 30 rats that were then randomly divided into the model control group (model group), BMSCs transplantation group (BMSCs group), and BMSCs transplantation combined with Jisheng Shenqi decoction group (combined group). Ten normal rats were used as the normal control group (normal group). The BMSCs and combined groups were injected with fluorescent-labeled BMSCs into the tail vein; the combined group was administered Jisheng Shenqi decoction at the same time; the normal and model groups were not treated. The liver function index and liver pathologic changes were observed at 4 weeks after treatment. The homing of BMSCs in liver tissue in each group was observed under fluorescence microscopy. The serum expressions of stem cell factor, hepatocyte growth factor, granulocyte colony-stimulating factor, and erythropoietin were detected by ELISA. The expressions of SDF-1 and CXCR4 proteins were detected by immunohistochemical staining. Results Under light microscopy, the degree of fibrosis and inflammatory activity was significantly improved in the BMSCs and combined groups compared with the model group. Compared with the normal group, the model group had significantly increased serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and γ-glutamine tanspeptidase and a decreased albumin concentration ( P< 0. 05); these concentrations were also significantly improved in the BMSCs and combined groups compared with the model group (P<0. 05). There were more homing BMSCs observed in the combined group than the BMSCs group (P<0. 05). Compared with the model group, the BMSCs and combined groups had increased expressions of stem cell factor, hepatocyte growth factor, granulocyte colony-stimulating factor, and erythropoietin; furthermore, the expressions of these factors were higher in the combined group than the BMSCs group ( P< 0. 05). Immunohistochemical analyses showed that the expressions of SDF-1 and CXCR4 proteins were upregulated in the BMSCs and combined groups compared with the model group, and were upregulated in the combined group compared with the BMSCs group ( P< 0. 05 ). Conclusions Jisheng Shenqi decoction activates the SDF-1/ CXCR4 biological axis, upregulates the expressions of related proteins and upstream regulatory factors, promotes the homing of BMSCs to the injured liver tissue, and significantly improves the liver function and pathological changes in a rat model of liver cirrhosis.

Abstract: Objective To investigate the effect of ShenQiWan on diabetic renal injury and evaluate whether the mechanism of ShenQiWan is to reduce endoplasmic reticulum stress via the protein kinase R-like endoplasmic reticulum kinase (PERK) pathway. Methods Twenty 12-week-old male ZDF ( fa / fa) rats were randomly divided into the model group (n= 10) and SQW group (n= 10). Seven male ZDF (fa / +) rats of the same age were used as the control group. The SQW group was given ShenQiWan decoction ( 8. 12 g / kg), whereas the control and model groups were given an equivalent volume of normal saline. During the intervention period, the general state of the rats was recorded, the fasting blood glucose concentration was measured regularly and the 24 h urinary microalbumin concentration was tested. To observe the pathological changes, paraffin sections of renal tissue were stained with periodic acid Schiff, Masson blue, and periodic acid methenamine silver-hematoxylin and eosin. Real-time PCR and western blot testing were conducted to detect the gene and protein expressions of the PERK pathway-related factors GRP78, PERK, eIF2α and ATF4 in the kidney. Results Compared with the other two groups, the model group showed slow weight gain, reduced body hair gloss and inactivity. The model group had a significantly higher fasting blood glucose concentration and 24 h urinary microalbumin concentration than the control and SQW groups ( P< 0.05). Morphological observation showed the glomerular capillaries were dilated, basement membrane was irregularly thickened, mesangial area was widened, and some glomeruli had segmental sclerosis in the model group compared with the control group. Renal tubular atrophy and renal interstitial fibrous tissue proliferation were also observed in the kidneys of the model group. These pathological changes were reduced in the SQW group. Real- time PCR and western blot analysis showed that the SQW group had significantly reduced expressions of GRP78, PERK, and eIF2α compared with the model group (P<0. 05); however, the ATF4 mRNA expression did not differ between the model and SQW groups. Conclusions Diabetic renal injury in ZDF rats is alleviated by ShenQiWan, and the mechanism may be downregulation of endoplasmic reticulum stress via the PERK pathway.

Abstract: Objective To observe the effect of long-term glucocorticoid (GC) administration on the metabolism and organs of normal rats. Methods Sixty clean-grade male KM rats ( body weight 32 ~ 35 g) were divided into four groups that were given topical urea ointment 1 g / d (control group), 0. 05% topical halometasone ointment 1 g / d ( topical halometasone group), 6 mg / ( kg·d) prednisone gavage ( prednisone group ), and 0.9 mg / ( kg·d ) subcutaneous dexamethasone (dexamethasone group), respectively, for 6 months. Metabolic variables ( including body weight, blood glucose and mean arterial pressure) were measured and evaluated at different times. After 6 months, the rats were euthanized and the pathological changes in the heart and liver tissues were evaluated. Results The metabolic variables of rats systemically treated with GC were significantly different compared with rats topically treated with GC; systemic GC administration caused accelerated weight gain, increased mean arterial pressure, increased fasting blood glucose concentration, and abnormal oral glucose tolerance, with the most significant changes seen in the prednisone group. Systemic GC administration caused obvious organ damage, comprising cell degeneration and fatty infiltration of heart tissue, and severe fatty infiltration, inflammatory infiltration, and lobular damage of liver tissue; the most serious organ damage was found in the dexamethasone group. Long-term topical GC administration had no significant effects on body weight, mean arterial pressure, fasting blood glucose concentration, and oral glucose tolerance, and did not cause organ damage in normal rats. Conclusions Long-term topical administration of halometasone ointment has less adverse effects and is safer than systemic administration of prednisone and dexamethasone. These findings provide important information regarding the clinical use of GC in patients.

Abstract: Objective To investigate the effect of yulangsan chalcone (YLSC) on the nuclear factor (NF)-κB signaling pathway in rats with myocardial ischemia / reperfusion injury (MI/ RI). Methods A rat model of MI/ RI was prepared by ligating the left anterior descending branch of the coronary artery. The extent of myocardial infarction was observed by double staining with Evans blue / TTC, and the serum concentrations of creatinine kinase (CK), CK-MB isoenzyme, and hydroxyproline were detected. Immunohistochemistry and western blot analyses were used to detect the protein expressions of NF-κB-inducing kinase (NIK), inhibitor of κB ( IκB), IκB kinase ( IκK) and NF-κB. Results YLSC reduced the extent of myocardial infarction in rats with MI/ RI; reduced the concentrations of CK, CK-MB isoenzyme, and hydroxyproline; inhibited the protein expressions of NIK, IκK and NF-κB; suppressed the enzyme activity of NIK and IκK; lessened the degradation of IκB and increased its expression. Conclusions YLSC exhibited protective effects in MI/ RI rats. The protective mechanism of YLSC may be related to a reduction in the extent of myocardial infarction, decrease in myocardial enzyme leakage, regulation of NIK/ IκK/ IκB/ NF-κB expressions in the inflammatory pathway, and reduction of the inflammatory response.

Abstract: Objective To investigate the effects of dexmedetomidine combined with sufentanil on lung ischemia- reperfusion injury (LIRI) in rats. Methods SD rats were randomly divided into the sham operation group, model group, sufentanil group, dexmedetomidine group and sufentanil+dexmedetomidine group (n= 6 mice per group), and rats in these groups were given 20 μg / kg sufentanil, 25. 2 μg / kg dexmedetomidine and 20 μg / kg sufentanil + 25. 2 μg / kg dexmedetomidine, respectively. The LIRI model was then established. The lung tissue structure was observed by HE staining and TUNEL staining, and the mitochondrial damage of lung cells was observed by electron microscopy. The levels of SOD and MDA in lung tissues were detected by ELISA, and the protein levels of LC3B, Beclin1, ATG5, HO-1 and Nrf- 2 in lung tissues were detected by Western blot. Results Sufentanil and dexmedetomidine alone or together improved lung tissue damage, reduced lung cell apoptosis, alleviated mitochondrial swelling of lung cells and decreased the expression of SOD and MDA in LIRI rats. The three treatments also decreased the protein expressions of LC3B-Ⅱ, Beclin1 and ATG5 and the ratio of LC3B-Ⅱ/ LC3B-Ⅰ and increased the protein expressions of LC3B-Ⅰ, Nrf-2 and HO-1 in LIRI rats. Among the three treatments, the combination of sufentanil and dexmedetomidine had the best performance. Conclusions Dexmedetomidine, sufentanil and the combination effectively improved LIRI in rats. Dexmedetomidine and sufentanil have a synergistic effect on improving LIRI in rats, and the mechanism might be related to the activation of the NRF-2/ HO-1 antioxidant stress pathway and inhibition of excessive autophagy.

Abstract: Objective Taking the congenital microcephaly and suspected epilepsy (mise)zebrafish mutant caused by spontaneous as a model, to study its inheritance pattern and phenotype-related mutation gene location. Methods By comparing the head width and eye area of normal and mutant zebrafish, the microcephaly and ommatidia traits of mutants were identified; the inheritance pattern of the mutation was determined by constructing a family. Genome resequencing combined with bulked segregation analysis (BSA) and kompetitive allele specific PCR ( kompetitive allele specific PCR, KASP)and Sanger sequencing were used to obtain the location of mutant genes. Results Compared with the wild type, the head and eye were significantly reduced at 3dpf, accompanied by convulsions and tremors. The mutant gene associated with phenotype was identified as terfa by gene mapping and verification. Conclusions This study uses whole-genome resequencing combined with linkage analysis to quickly locate mutant genes. It laid the foundation for the locational cloning of zebrafish mutants and the functional analysis of genes related to abnormal development of the nervous system.

Abstract: Objective To establish a simple and fast paraffin section technique and staining method suitable for use with three-dimensional (3D) cell culture models and to provide a convenient pathological technology platform for the study of the morphology, function, and application of 3D cell culture models. Methods HepG2 cells or/ and LX-2 cells were cultured into 3D multicellular spheroids using an ultra-low attachment surface culture plate, and paraffin sections were made. Hematoxylin and eosin ( HE) staining, immunohistochemical staining, and immunofluorescence staining were performed to detect the histological and morphological characteristics and protein expression of the multicellular spheroids. Results A rapid paraffin sectioning method suitable for 3D cell culture models was established. The prepared sectioned cell spheroids had complete structure, clear cell boundaries, and good antigen activity. The morphological structure and the expression and distribution of the proteins of 3D cell culture models could be accurately detected by HE staining, immunohistochemical staining, and immunofluorescence staining. Conclusions The establishment of a rapid paraffin sectioning method has enriched the research method available for 3D cell culture models and could promote their application in basic research, translational medicine, and drug development.

Abstract: Objective To investigate the effect of BAPN combined with AngII ( BAPN + Ang II) on the phenotypic changes of macrophages in the aorta of mice with aortic dissection. Methods Searching for relevant core genes and related biological functions and signaling pathway profiles through transcriptome microarrays related to aortic coarctation. We then applied CIBERSORT to analyze the proportion of various types of cells in the aorta. Last, we conducted immunofluorescence, Western blot, and enzyme-linked immunosorbent assays to study the phenotypic changes of M1 and M2 macrophages in aortic dissection. Results GSE147026 found a total of 930 differential genes related to aortic dissection. The biological functions of these genes involve mainly the adhesion of leukocytes to cells, extracellular structure organization, macrophage activation, extracellular matrix organization, and leukocyte migration. Their molecular functions are concentrated mainly in the membrane: microdomains, membrane rafts, adhesion spots, cell-substrate junctions, and collagen extracellular matrix, and their biological processes focus mainly on integrin binding, Toll-like receptor binding, scavenger receptor activity, receptor activity, and extracellular matrix structure components. The CIBERSORT analysis revealed that naive B cells and M1 macrophages exhibited higher infiltration levels in aortic dissection tissues, activated NK cells displayed higher infiltration levels in normal aortic tissues, and M0 and M2 had higher infiltration levels in aortic dissection tissues; however, these differences did not reach statistical significance. No other cell types presented a significantly different level of abundance between normal aorta and aortic dissection. Compared with the normal group, the protein expression levels of iNOS, CD206, IL-6 and IL-10 were the highest in the BAPN+Ang II group, followed by the BAPN group, with the Ang II group having the lowest levels. Conclusions Both M1 and M2 macrophages accumulate in the aorta of aortic dissection mice; their relative accumulation levels in our groups were as follows: Among them, the BAPN + AngII group had the largest accumulation, followed by BAPN and the least AngII.

Abstract: Objective CRISPR/ Cas9 technology was used to knock out glutathione S-transferase zeta 1 (GSTZ1) and fumarate acetoacetate hydrolase (FAH) in human LO2 liver cell line, to explore the effect of GSTZ1 and FAH on the growth, proliferation and migration of hepatocytes. Methods Guide RNAs ( sgRNAs) targeting GSTZ1 and FAH genes were constructed, and co-transfected with CRISPR/ Cas9 vector into LO2 cells. Three cell lines GSTZ1- / - , FAH- / - and FAH- / - / GSTZ1- / - were identified by sequencing and Western blot. The cells were used for further analysis, including the ability of hepatocyte clone formation, cell proliferation and cell migration. Results Three cell lines GSTZ1- / - , FAH- / - and FAH- / - / GSTZ1- / - were successfully established. Compared with wild-type cells, all of three edited cell lines showed higher ability of proliferation, clone formation and migration. FAH mutation has limited effect on cell phenotype, while GSTZ1 deletion greatly improved activity of the hepatocytes. The dual-gene knockout cells demonstrated moderate activity between two single mutants. Conclusions FAH/ GSTZ1 dual-mutated hepatocyte cell lines were established for the first time, which provides a new cell model for the study of tyrosine metabolism pathway and hereditary tyrosinemia type I (HT1) therapy.

Abstract: Objective To analyze the components of Lonicerae japonicae flos ( the dried flower bud or newly bloomed flower of Lonicerae japonicae Thunb. ) water extract (LJFWE) and its potential mechanism on improving sepsis, and to verify its effects on sepsis in vitro using RAW 264. 7 murine macrophages cells. Methods (1) UPLC-QE Orbitrap MS was used to identify LJFWE compounds and search for the target genes on improving sepsis. (2)The multiple disease databases were used to build a sepsis target database. (3) RT-PCR was used to verify the core genes adjusted by LJFWE in sepsis, after the establishment of the RAW 264. 7 cell sepsis model. Results 23 active components on improving sepsis were obtained under the UPLC-QE Orbitrap MS in positive and negative ion modes with comparing the local database and literature, including Luteolin, kaempferol, quercetin, loganin and caffeic acid in LJFWE. MAPK8、TP53、RELA、 MAPK1 and MYC were predicted as the key targets. RT-qPCR results showed that LJFWE down-regulated the expression of inflammation-related factors ( IL-1β, IL-6, IL-10, iNOS, TNF-α) and five key target genes (MAPK8, TP53, RELA, MAPK1, MYC) compared with the model group. Conclusions Luteolin, kaempferol, quercetin, loganin, and caffeic acid may be the effective ingredients in the treatment of sepsis in LJFWE. MAPK8,TP53,RELA,MAPK1 and MYC and inflammation-related factors ( IL-1β, IL-6, IL-10, iNOS,TNF-α) may be the key targets of LJFWE in the treatment of sepsis. This study provided a theoretical basis for further verification of the mechanism of Lonicerae japonicae flos in the treatment of sepsis.

Abstract: Objective To investigate the effect of recombinant BPI on the inflammatory response and TLR4 / NF- κB signaling pathway in mice infected with Mycoplasma pneumoniae. Methods BALB/ c mice ( n= 67) were randomly divided into the control group, M. pneumoniae (MP) model group and high-, medium- and low-dose groups of recombinant BPI protein. The MP model was established by nasal drip of 1×10⁶ CCU/ mL (100 μL) MP bacteria solution for 4 days. After successful modeling, mice in each treatment group were injected with 1. 5 mL of recombinant BPI protein solution with concentrations of 0. 45,0. 3 or 0. 15 mol / L through the lumbar vein. Mice in the control group and model group were injected with the same amount of normal saline through the lumbar vein. All mice were treated for 4 weeks. The lung tissue and serum of mice was collected at the last administration, and the lung index and dry wet ratio were calculated; the pathological changes of lung tissue were observed by HE staining method and the pathological score of lung tissue was determined. Serum inflammatory factors were detected by ELISA and the mRNA expressions in lung tissue were detected by RT-PCR; Western blot was used to detect the expression of TNF-α, IL-6 and IL-1β. Results Compared with the MP model group, the BPI protein group showed a decreased lung index (P<0. 05), increased dry wet ratio (P<0. 05), and decreased serum levels of TNF-α, IL-1β and IL-6 (P<0. 05). Compared with MP model group, the mRNA and protein expressions of TLR4 and NF-κB p65 in lung tissue of mice in recombinant BPI group were significantly down-regulated (P<0. 05), and the mRNA and protein expressions of I-κBα were significantly up-regulated ( P< 0. 05). Conclusions Recombinant BPI protein may inhibit the production of TNF-α, IL-1β and IL-6 by regulating the TLR/ NF-κB signaling pathway, so as to reduce the pulmonary inflammatory response in mice.

Abstract:Spinal cord injury is a central nervous system disease with high mortality and disability rates and poor reversibility. Spinal cord injury is a serious worldwide public health problem, and has a complex physiopathologic mechanism that remains unclear. Autophagy is a highly conserved cellular process that is essential in the steady state of spinal cord neurons with terminal differentiation and leads to cell survival or death in different environments. In recent years, much attention has been paid to autophagy and relevant signaling pathways regulating autophagy. Clarifying the chain relationship of spinal cord injury, signaling pathways, and autophagy may aid in the understanding of the dynamic pathological changes that occur after spinal cord injury and clarify whether therapeutic activation or inhibition of autophagy is helpful for functional recovery after spinal cord injury. This paper reviewed the latest research progress on the mechanism of autophagy and relevant signaling pathways in spinal cord injury to provide new ideas for targeted therapy.

Abstract:Precancerous lesions of gastric cancer (PLGC) are a key link between chronic atrophic gastritis and gastric cancer, and pre-gastric cancer intervention is significant for impacting gastric cancer. MNNG solution, in combination with a multi-factor modeling method , is a common method applied to the study of PLGC. However, at present, the prospects of MNNG solution use are still unclear, as the concentration and its factors are specific. This manuscript presents nearly five years’ worth of data from PLGC production in rats, summarizes four MNNG solution composite method with high usage rates, and discusses the model research progress in pre-stomach cancer rats in the context of MNNG solution concentration, administration, and multi-factor combination to guide the development of model method, animal experiments and further research on PLGC.

Abstract:With the discovery of immune checkpoint molecules and the subsequent explosion of related research, immune checkpoint-blocking therapy has become a key topic in tumor immunotherapy. Immune checkpoint T-cell immunoglobulin mucin 3 (TIM-3) is a transmembrane protein belonging to the TIM family. It is expressed in a variety of immune cells and non-immune cells and is an important molecule for negative immune regulation. TIM-3 not only can reduce inflammation, mediate the immune tolerance of organ transplantation, and inhibit autoimmune disease, but also can cause tumor immune escape. Furthermore, it can activate negative immune regulation pathways by interacting with ligands and can inhibit the activation of immune cells to downregulate the killing effect of the immune system on tumors. By blocking the binding between TIM-3 and its ligand, the anti-tumor immune activity of immune cells can be restored, the size of tumor foci can be reduced, and the tumor clearance rate can be improved. This article briefly reviews the research on TIM-3 in tumor immunity and tumor immunotherapy conducted in recent years.

Abstract:Type I hypersensitivity is a common disease that is mainly mediated by IgE antibody molecules, resulting in a series of local or systemic reactions. To effectively treat type I hypersensitivity, the key research direction is the development of new diagnostic technologies and immunotherapies. The newly discovered diagnostic techniques include allergen component deterministic diagnosis, eosinophil cationic protein detection, and the basophil activation test. Immunotherapy has also developed rapidly, with researchers from around the world developing a variety of new specific and non-specific immunotherapies and technologies. This article summarizes the recent developments in type I hypersensitivity diagnosis technology and immunotherapy as a reference for future research.

Abstract:Ischemic stroke, which has caused serious disease burden due to its high incidence rate, disability rate and mortality rate, is one of the key diseases that medical research and development personnel are concerned about. However, the conversion rate of preclinical research result of stroke to clinic is low, which highlights the urgent need for animal model optimization. Nonhuman primates ( NHPs) have higher similarities with humans in brain anatomy and physiology. Therefore, building models with NHPs is expected to promote the transformation from preclinical research to clinical treatment of ischemic stroke. This paper reviews the modeling method , evaluation indexes and model application progress of stroke NHPs model, discusses the advantages and disadvantages of recent models and evaluation method , and looks forward to the difficulties and possible development direction of NHPs model research in the future.

Abstract:Diabetic cardiomyopathy (DCM) is a cardiomyopathy that presents as cardiac structural and functional damage caused by sustained high blood glucose. DCM is one of the most common diabetic complications. It significantly increases the risk of heart failure in diabetic individuals independent of other cardiovascular diseases such as hypertension and coronary heart disease. The development of DCM experimental models will be helpful for investigating the in-depth molecular mechanisms of DCM as well as for developing new diagnostic and therapeutic approaches for DCM. In this review, we summarize the common animal models and in vitro models of DCM. The advantages of human induced pluripotent stem cell-derived cardiomyocytes in establishing DCM models are introduced to provide an important new insight for studying DCM.

Abstract:Ferroptosis is a novel type of programmed cell death that has recently attracted increasing attention. Studies have suggested that ferroptosis is involved in the tissue damage caused by paraquat poisoning. This review summarizes the mechanism of ferroptosis and its role in tissue damage caused by paraquat poisoning, providing a theoretical basis for its further study.

Abstract:Alzheimer’ s disease (AD) is a common degenerative disease of the central nervous system with unknown etiology and pathogenesis that has a large negative effect on the lives of patients and their families. The successful establishment of an animal model of AD in line with the occurrence and progression of human disease is particularly important for the exploration of the pathogenesis of the disease and the development of therapeutic drugs or other interventions. Therefore, to provide a reference for researchers in related fields to select appropriate animal models and to contribute ideas for the construction of new animal models and the development of new model index evaluation method , we reviewed the technical method , functional principles, and current applications of animal models of AD globally, summarized the evaluation method of relevant indicators, analyzed the advantages and disadvantages of transgenic and non- transgenic models of AD, and generalized the application prospects and characteristics of cognitive behavioral method, immunological method and imaging method.