Abstract:Objective We investigated the effects of barbaloin on podocyte function and on the nicotinamide adenine dinucleotide phosphate oxidase 4 (NEX4)/reactive oxygen species (ROS)/p38 mitogen activated protein kinase signaling pathway (p38 MAPK) in rats with diabetic nephropathy (DN). Methods The rats were fed high-sugar and high-fat diet for 4 weeks and injected 40 mg/kg STZ intraperitoneally establisha a DN rat model and randomly divided into a model group, a positive control group, dose dependent (low, medium, and high) experimental groups, and a normal group in which the rats were not treated. The positive control group was given 9.45 mg gliguidone per kilogram per day (kg·d) for six weeks. The low, medium, and high dose experimental groups were given 10, 20, and 40 mg/(kg·d) barbaloin, respectively, by gavage for six weeks. The normal group and model group were given equal volume distilled water by gavage for six weeks. Fasting blood glucose levels were measured using a blood glucose meter, and the levels of interleukin-1β (IL-1β) and serum tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was used to observe renal morphology. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) in kidney tissue were detected using commercial SOD, MDA and ROS assay kits; and the levels of NADPH oxidase 4 (NOX4), p38 mitogen-activated protein kinase (MAPK), phospho-p38 MAPK, the glomerular podocyte gap transmembrane protein Nephrin, and Podocin were detected by western blot. Results Before administration, compared with the normal group, the fasting blood glucose level of the model group, the positive control group, and the low, medium, and high dose experimental groups increased (P <0. 05). After administration, glomerular hypertrophy, mesangial thickening, glomerular basement membrane thickening, and interstitial inflammatory infiltration were observed in the model group. In the low and middle dose group, glomerular hypertrophy was relieved gradually, the mesangial hyperplasia was mild to moderate, and the dilation of renal tubules was slowed down. In the high dose experimental group, the renal tissue was normal in morphology and clear in structure, and the shapes of the glomerulus and renal tubules were regular. Compared with the normal group, the levels of fasting blood glucose, and IL-1β, serum TNF-α, MDA, ROS, NOX4, and phospho-p38 MAPK proteins in kidney tissue of the model group increased (P < 0. 05), and the levels of SOD, SOD/ MDA, Nephrin, and Podocin proteins in kidney tissue decreased (P <0. 05). Compared with the model group, the levels of fasting blood glucose, and IL-1β, serum TNF-α, MDA, ROS, NOX4, and phospho-p38 MAPK proteins in kidney tissue of the positive control group and high dose experimental group decreased (P < 0. 05); and the levels of SOD, SOD/MDA, Nephrin, and Podocin proteins in kidney tissue increased (P <0. 05). The levels of fasting blood glucose, and IL-1β, serum TNF-α, MDA, ROS, and NOX4 proteins in kidney tissue of the middle dose experimental group decreased (P < 0. 05); and the levels of SOD, SOD/ MDA, Nephrin, and Podocin proteins in kidney tissue increased (P < 0. 05). The levels of fasting blood glucose, and IL-1β, serum TNF-α, MDA, and NOX4 proteins in kidney tissue of the low dose experimental group decreased (P <0. 05); and the level of SOD in kidney tissue increased (P < 0. 05). Compared with that before administration, the fasting blood glucose level of the positive control group, and the experimental (low, medium, and high dose) groups decreased after administration (P <0. 05). Conclusions Barbaloin can inhibit the NOX4/ROS/p38 signaling pathway to achieve anti-inflammatory actions and podocyte recovery.

Abstract:Objective We investigated the effects of curcumin on the Kelch-like ECH-associated protein-1 (Keap1) / antioxident responseelement (ARE) signaling pathway and on bile acid hepatointestinal circulation in hepatoma model mice. Methods C57BL/6 mice were randomly divided into control group, model group, a low dose ( 10 μg/g) curcumin group, a medium dose (20 μg/g) curcumin group, a high dose (30 μg/g) curcumin group, and a cisplatin (10 μg/g) group, with 12 mice in each group. except for the control group, the other groups were given diethylnitrosamine to induce the establishment of liver cancer models, After grouping, the pathological morphology of liver tissue was detected by hematoxylin eosin (HE). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), and total bile acid ( TBA) serum contents of the mice were measured. The levels of serum interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) of mice were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of the Keap1/ARE pathway related proteins, Keap1 and nuclear factor erythroid 2 related factor 2 (Nrf2), were detected by quantitative real-time polymerase chain reaction (qRT-PCR) fluorescence analysis and Western blot. Results Compared with the control group, the liver tissue of mice in the model group showed canceration and other pathological damage. The levels of serum ALT, AST, TB, TBA, IL-6, TGF-β1, and Keap1 mRNA and protein in liver tissues were significantly increased (P <0. 05), and the levels of Nrf2 mRNA and protein were significantly decreased (P <0. 05). Compared with the model group, the liver tissue pathological damage of mice in the low, middle and high dose curcumin groups, and in cisplatin group was alleviated; the levels of serum ALT, AST, TB, TBA, IL-6, TGF-β1, and Keap1 mRNA and protein in liver tissue were decreased; and the levels of Nrf2 mRNA and protein were increased, with each index changing in a gradient fashion with the increase of curcumin dose (P <0. 05). There was no significant difference between the high dose curcumin group and the cisplatin group of mice (P >0. 05). Conclusions Curcumin can reduce liver damage and improve the circulation of bile acid in the liver and intestine. This may be achieved by the down-regulation of the expression of Keap1 and the activation of downstream ARE signals.

Abstract:Objective To investigate the effects of bortezomib ( Bor) on nuclear factor _κB ( NF-_κB) and inflammatory damage in ATDC5 cells induced by interleukin-1β (IL-1β). Methods ATDC5 cells were treated with (0, 5, 15, 25, 35, 45, 55) nmol/L Bor for 48 hours, and CCK-8 was used to determine the cytotoxic concentration of Bor. ATDC5 cells were co-cultured for 48 hours with (0, 1. 0, 5. 0, 12. 5, 25. 0) nmol/L Bor and 10 μg/mL IL-1β. CCK-8 was used to detect cell proliferation and apoptosis was detected by flow cytometry. IL-1β in supernatant was detected using an enzyme-linked immunosorbent assay (ELISA), and the levels of NF-_κB, B-cell lymphoma/leukemia-2 proto oncogene (BcL2) and BcL2-related X protein (BAX) were determined by Western blot. Results There was no significant difference in (0, 5, 15, 25) nmol/L Bor group (P >0. 05). Compared with the 0 nmol/L Bor group, the cell survival rate of the 35, 45, and 55 nmol/L Bor groups was reduced (P <0. 05). A concentration of ≤25 nmol/L Bor was non-toxic to the cells. Compared with the 0 nmol/L Bor group, the cell survival rate and BcL2 protein level in the IL-1β group was decreased (P <0. 05), and the apoptosis rate, IL-1β level in the supernatant, and NF-_κB and BAX protein levels were increased (P <0. 05). With increasing Bor dose, the cell survival rate and the level of BcL2 protein in cells gradually increased (P <0. 05), while the apoptosis rate, the level of IL-1β in supernatant, and the levels of NF-_κB and BAX proteins in cells gradually decreased (P <0. 05) in a dose-dependent manner. Conclusions Bor can inhibit apoptosis and reduce the levels of inflammatory factors, thereby reducing inflammatory damage to ATDC5 cells induced by IL-1β, which may occur via inhibition of the NF-_κB pathway.

Abstract:Objective We investigated the infection of SARS-CoV-2 in laboratory animals. Methods The double-antigen sandwich ELISA method was used to detect SARS-CoV-2 antibodies in the serum samples from five laboratory animal production facilities in 2020, including 90 mice of 25 strains, 38 rats of 5 strains, 20 guinea pigs, 27 rabbits of 3 strains and 5 beagle dogs. Results A total of 90 mice, 38 rats, 20 guinea pigs, 27 rabbits, and 5 beagle dogs sent for testing by various experimental animal production units in 2020 were tested for SARS-CoV-2 antibodies by double antigen sandwich ELISA, and the result were all negative. Conclusions Preliminary studies have not confirmed the existence of SARS-CoV-2 in laboratory animals.

Abstract:Objective We investigated the effect of mothers against decapentaplegic homolog 6(Smad6) on the migration and epithelial-mesenchymal transition of human glioma cell lines by targeting microRNA-186 (miR-186). Methods The expression of miR-186 and Smad6 at the mRNA and protein level ( for Smad6) was determined by RT- qPCR and / or Western blot in astrocytes and glioma cells. The cells were divided into four groups: a blank control group (U251), a mimic group (miR-186 mimics), a plasmid group (pc-smad6), and a co-transfection group (miR-186 mimics + pc-smad6). The expression of Smad6, E-cadherin, and Vimentin at the mRNA and protein level was determined by RT- qPCR and Western blot in each group. Migration ability was measured using a wound healing experiment. Results Compared with astrocytes, the expression of miR-186 in human glioma cell line U251 decreased significantly, while the expression of Smad6 mRNA increased significantly (P <0.05). Compared with the control group, the expression level of the Smad6 protein in the miR-186 mimic group decreased significantly, while the level of the Smad6 protein in the pc-smad6 group increased significantly (P <0.05). Compared with the pc-smad6 group, the expression level of the Smad6 protein in the miR-186 mimics + pc-smad6 group significantly decreased (P <0.05). Compared with the control group, the migration ability of the miR-186 mimics group decreased significantly, while the pc-smad6 group’s migration ability was enhanced. Compared with the pc-smad6 group, the migration ability of the miR-186 mimics + pc-Smad6 group decreased significantly (P <0.05). Compared with the control group, E-cadherin expression in the miR-186 mimics group increased significantly, while Vimentin protein expression decreased significantly (P <0.05).The expression of the two molecules in the pc-smad6 group was the opposite (P <0.05). Compared with the pc-smad6 group, vimentin expression in the miR-186 mimics + pc-smad6 group decreased significantly, while E-cadherin expression increased significantly ( P <0.05). Conclusions miR-186 may regulate migration and epithelial-mesenchymal transition of glioma cells by targeting Smad6.

Abstract:Objective We investigated mechanisms associated with Polygonum perfoliatum L. extract in relieving a 9-month-old APP / PS1/ tau three-transgenic Alzheimer’s disease model in mice. Methods Male APPSwe / PS1M146 V/ tauP301 L 3xTg-AD 3xTg-AD mice and their background C57BL/ 6J mice were randomly divided into four groups, with 12 mice in eachper group, respectively: a control group (normal saline), a three-turn model control group (normal saline), a three-turn model anesthesia group (normal saline + sevoflurane), and a three-turn model administration group (normal saline + sevoflurane + Polygonum perfoliatum L. extract). All mice were injected with isovolumic saline or 0. 1 μg/4 μL of Polygonum perfoliatum L. extract through the lateral ventricle for 10 consecutive days. The control group inhaled two hours of oxygen, and the anesthetized group and the administration group inhaled two hours of sevoflurane. At 24 hours after the end of anesthesia, six mice in each group were tested for spatial learning and memory in a Morris water maze. Fresh hippocampal tissue was obtained by decapitation from the remaining mice, prepared into a homogenate, and b-amyloid peptide (Aβ) aggregation (Aβ, Aβ1-40, Aβ1-42) was detected by Western blot and by tau protein phosphorylation. The phosphorylation levels of all associated loci (Serine 396, Serine 262 and Threonine 231) were checked as well. The expression of mitochondrial apoptosis signaling pathway genes, including B-cell lymphoma-2 (BcL-2), BcL-2-associated X protein (Bax) and Cysteine-requiring Aspartate Protease (Caspase-3) was detected by Real-time PCR. Results Morris water maze experiments show that sevoflurane has no effect on learning and memory ability in mice, but it does have potential neurotoxicity in mice. Extracts of Polygonum perfoliatum L. can reduce Aβ aggregation and tau protein phosphorylation states in three-transformation mice. Compared with the three-turn model anesthesia group, BcL-2 expression was decreased and Bax and Caspase-3 expression was enhanced in the three-turn model administration group. Conclusions Polygonum perfoliatum L. extract can alleviate mitochondria-associated apoptotic signaling pathways induced by sevoflurane anesthesia, as well as reduce Aβ aggregation, decrease tau protein phosphorylation, and inhibit the apoptosis of mouse hippocampal neurons.

Abstract:Objective The inbred transgenic nude mice with green fluorescent protein gene (GFP nude mice) line that we established have played an important role in tracing studies of the glioma microenvironment, but no study has yet reported its mechanism and effect in treating bone resorption complications after autologous cranioplasty. Our purpose in this article is to analyze the phenotype of GFP nude mouse skull cells cultured in vitro to lay the foundation for preparing tool cells for the treatment of skull resorption. Methods We selected GFP mice within three days after birth. Under sterile conditions, bilateral parietal bones with periosteum were isolated and cut into small 1 mm² pieces, and then placed in 1640 medium with fetal bovine serum. We then incubated the samples in a 5% CO2 incubator. Those cells that crawled out of the bone slices were collected for short-term subculture and relevant analyses. Results Observation of primary (P0) and secondary (P1, P2) cells indicates that the passage time in which cells grow to cover 90% of the bottom of a 60 mm dish is about 6~ 8 days, with a sampling calculation of 2. 3×10⁶~2. 5×10⁶ cells per dish. The cell morphology is mainly fibrous, but also star-shaped and dendritic. All cells emit green fluorescence under a fluorescent microscope, which is consistent with that under a white light microscope. Marker protein detection showed that BMP-6+ osteoblasts and CD206⁺、CD68⁺ macrophages coexist in the entire cell population. Conclusions Based on our skull regeneration studies, macrophages must also be involved in maintaining environmental homeostasis, in addition to the osteoblastic progenitor cell role as a starting cell. Successfully cultured P0, P1, and P2 third-generation cells meet this need, and are all expected to be further used as a tool cell in skull regeneration research.

Abstract:Objective To observe the effect of miR-424-5P on Src-YAP signaling and the proliferation of colon cancer cells. Methods Colon cancer HT-29 cells were used. Exogenous up-regulation of miR-424-5P was achieved in HT- 29 cells by transfection and a blank group (Blank group), an empty vector group (NC group) and an overexpression group (miR-424-5P-OV group) were prepared. RTFQ-PCR was used to detect the level of miR-424-5P. MTT assays were used to detect cell viability. The nuclear distribution of YAP was detected by immunofluorescence. Western blot was used to detect the levels of Src, YAP, LATS1 and their phosphorylation. Results Compared with the NC group, the miR-424-5P RNA level in the miR-424-5P-OV group was significantly increased (P <0.01). The overexpression of miR-424-5P significantly reduced the viability and colony-forming ability of HT-29 cells (P <0.01). In the blank and NC groups, YAP was mainly localized in the nucleus, with little cytoplasmic distribution, while in the miR-424-5P-OV group, YAP showed obvious cytoplasmic and nuclear distribution. Overexpression of miR-424-5P significantly up-regulated p-YAP and p-LATS1 protein levels (P <0.01) and down-regulated p-Src protein levels (P <0.01). Conclusions Overexpression of miR-424-5P can inhibit the proliferation of colon cancer HT-29 cells, which may be related to weakened Src-YAP signaling.

Abstract:Objective To study the effect of triptolide-loaded exosomes in prostate cancer model mice. Methods A mouse model of prostate cancer was established and three groups of mice were prepared: control, TPL and exo-TPL groups. The MTT method was used to observe inhibition of cell proliferation. qPCR was used to detect the expression of NF-_κB and p53. On the 8th , 11th , 15th and 18th day after model induction, mice were administered TPL or exo-TPL. The volume and mass of tumors were observed and the survival time was recorded. The blood concentration and tissue distribution of triptolide were observed in the different groups. Results Compared with the TPL group, the inhibition of RM-1 prostate cancer cell proliferation was significantly increased in the exo-TPL nanoparticle group. The mRNA level of NF-_κB was significantly decreased, while that of p53 was significantly increased. The tumor volume and mass in the exo-TPL nanoparticle group were significantly smaller than those in the TPL group, and the survival time was prolonged. Compared with the TPL group, the exo-TPL nanoparticle group maintained higher concentrations of triptolide in blood and tissue. Conclusions Compared with TPL treatment, exo-TPL was more effective at suppressing prostate cancer.

Abstract:Objective To evaluate an apex semi-barbed absorbable suture localization device for small pulmonary nodules. Methods Twenty-one pig lungs were evenly divided into three groups: a semi-barbed absorbable suture group, a microcoil group, and a hookwire group. Semi-barbed absorbable sutures, microcoils, and hookwires were used in respective groups for lung puncture localization. Success of localization was then assessed, and the maximum anchoring force of the localized object was tested by means of a hand-drawn tension frame. All localization operations are performed using a " pre-filled" localization method . Six experts evaluated the three groups. Results All 21 positioning operations in the three groups were successful. The maximum anchoring force of the apex semi-barbed absorbable suture group was significantly better than that of the microcoil group [(1.089±0.288) N vs (0.066±0.015) N, P = 0. 000] and the hookwire group [(1.089±0.288) N vs (1.190±0.279) N, P = 0. 519]. All six experts considered that the flexibility of the absorbable apex semi-barbed suture was similar to that of the microcoil, which was significantly better than that of the hookwire. Conclusions Apex semi-barbed absorbable sutures for localization at small nodules in the lungs exhibit strong anchoring force, good flexibility, low dislocation probability, and no risk of metal residue, and have good potential for clinical application. Further evaluation is warranted.

Abstract:Objective We explored the method and techniques of preparing frozen sections using different mice tissues as our experimental animal materials, to improve frozen section quality, and to increase the serviceability of these techniques for the non-clinical safety evaluation of monoclonal antibodies. Methods The heart, liver, spleen, lung, kidney, and brain tissues of healthy NIH mice were collected, embedded, frozen, and sliced using a Leica CM1950 thermostatic frozen microtome, and then stained by hematoxylin and eosin dye and sealed. Results The slices were observed by light microscopy, and the result show no fold, no knife marks, no damage, and no excessive ice crystals. The cell morphology was clear, with the nucleus and cytoplasm clearly colored, and staining was good. Conclusions In the process of making frozen slices, strict controls from the aspects of collecting, embedding, quick-freezing, temperature selection, and thermostatic frozen sectioning should be carried out. However, different tissues have differences according to their own characteristics, and should be treated differently. In addition, to prepare high-quality frozen sections, and to better serve the non-clinical safety evaluation of monoclonal antibodies, we collectively need a high sense of responsibility and patience while mastering key technical points.

Abstract:Compared with developed countries, the use of laboratory animals for scientific research in China is relatively recent. In the past 40 years, a standardized system of the use of laboratory animals has been constantly improved, which has improved the quality of biomedical research. However, some problems in the writing of standardized documents still persist. To improve the standardization of laboratory animal protocols and to promote better adherence to such standards, we summarize and analyze common problems in standardized documents for the use of laboratory animals. We provide correct examples using the basic framework of standard documents and according to the requirements of GB/ T 1.1 -2020

Abstract:Through understanding the significance and necessity of legislation for the use of laboratory animals, this paper makes a comparative analysis of the current situation of laboratory animal legalisation in several developed countries. Based on the problems and shortcomings of the Chinese legal system for managing laboratory animals, it then provides constructive suggestions for developing the legal system to protect laboratory animal welfare and to improve the quality of laboratory animal research in China. For example, we suggest enacting more detailed standards, building suitable management mechanisms, and strengthening the power of legal supervision. With a strategy in learning and comparing the legal system of several developed countries, in order to construct a legal system for laboratory animal field that better suits China’s national conditions, in line with China’s economic level.

Abstract:The Animal biosafety level 3 laboratory is a basic support platform of the national biosecurity system for responding to emerging and re-emerging communicable disease. It is also an important hardware foundation for studying the biological characteristics, prevention, and therapeutic tools of the novel 2019 coronavirus. In the emergency operation associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the development of knowledge of the virus, systematic and standardized biosafety management measures are essential for the efficient and orderly operation of the Biosafety Laboratory, and are critical in preventing the occurrence of accidents in the laboratory. This article discusses the biosafety management of the urgent development of SARS-CoV-2 experimental activities in the Animal biosafety bevel 3 baboratory, and aims to provide ideas for emergency management of related laboratories.

Abstract:Pathogenic microorganisms have become a crucial chip in the world’ s developed economies game of coexistence in international biosafety. Due to the present pandemic, an important strategic resource for this country needs to be developed during this adjustment period. However, the preservation institutions previously built in China’s early stages are now unable to meet the needs of the current situation. Under a new integrated plan from the National Health Commission, the Institute of Laboratory Animal Sciences of the Chinese Academy of Medical Sciences has established a National Pathogenic Microorganism Preservation Center, which provides a strong guarantee for the management, development, and utilization of microbial resources in China. In this paper, the construction plan and implementation process of the National Pathogenic Microorganism Preservation Center is expounded upon from the aspects of hardware facilities, management systems, and personnel teams, so as to provide reference for the construction of a standardized and informationized pathogenic microorganism preservation institution.

Abstract:Arginase II has evolved from ancestral genes in early life forms. It converts L-arginine to urea and ornithine to maintain physiology. Excessive arginase II activity in mammals is associated with cardiovascular and chronic inflammation diseases. Four aspects of this elevated activity may be involved in these disease states. First, excessive arginase II activity reduces the supply of L-arginine needed by nitric oxide (NO) synthase to produce NO. Second, excessive production of ornithine leads to disrupted vascular structure and neural toxicity. Third, arginase II over-activity in certain signaling pathways leads to increased inflammation. Forth, arginase II promotes the macrophage inflammatory response (M1 macrophage). Here, we review the role of arginase II in cardiovascular diseases and macrophages and in oxidative stress and inflammation mechanisms. We also discuss targeting arginase II as a promising therapeutic strategy.

Abstract:Aging of the global population is a critical public health issue. Immunosenescence is a core mechanism of aging. The herpes virus, cytomegalovirus (CMV), can establish lifelong latency in bone marrow stem cells after its entry into a human host. Cytomegalovirus latency is ubiquitous in aging populations and cytomegalovirus seropositivity is close to 100% in elderly populations. In addition, latent CMV in bone marrow stem cells can chronically induce immune responses through differentiation-dependent reactivation. The process of reactivation causes expansion of a large proportion of CMV- specific T cell clones with reserve na?ve T cells being gradually consumed. Thereafter, the diversity of adaptive T cells is reduced and inflammatory cytokines are consistently expressed at low levels, both of which are part of the core mechanism of immunosenescence. However, it is difficult to trace CMV latency and low level reactivation in bone marrow stem cells. The development of single cell-based RNA sequencing technology, however, enables the mechanism of latent CMV activation in bone marrow stem cells to be investigated in detail.

Abstract:Type 2 diabetes mellitus (T2DM) is a chronic disease with a high incidence in China. It occurs due to a relative lack of insulin because of insulin resistance and islet β-cell dysfunction. Type 2 diabetes is a progressive disease, and its dependence on exogenous glycemic control increases over the development of its natural course, leading to multiple tissue and organ diseases and causing various secondary complications. Traditional treatment relies heavily on drugs, yet oral drugs and exogenous insulin can only temporarily maintain blood glucose or temporarily improve insulin sensitivity; however, the disease cannot be cured fundamentally. With the deepening of stem cell research, the self-renewal and directional differentiation potential of stem cells have opened up new ideas for repairing damaged tissues and restoring islet function, thus treating diabetes. This article reviews the method, advantages, disadvantages, and research progress of different types of stem cells in the treatment of type 2 diabetes. We hope to provide reference for the study of the pathogenesis of diabetes and its complications, and for applying stem cell transplantation technology to restore insulin independence, as well as to establish an evaluation of the safety and effectiveness of stem cell therapy.

Abstract:Variations in the LMNA gene, which encodes lamin A, cause a wide range of genetic disorders. More than 900 LMNA variations have been found, which cause a variety of laminopathies with different phenotypes, such as mandibuloacral dysplasia, Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome. To better understand these laminopathies and to screen for therapeutic drugs, a series of mouse strains with LMNA variations have been established. These mouse models provide valuable tools for understanding LMNA function and its role in growth and development. Here, we review mouse models of laminopathies and we discuss their significance in progeria and physiological aging.

Abstract:Coronavirus disease 2019 (COVID-19) is a type of acute infectious pneumonia. The initial symptoms of infected patients are faintness, cough, and fever. Patients may gradually develop more serious symptoms such as dyspnea. COVID-19 transmission route, occurrence and development, vaccine development, and treatment remain to be fully clarified. Animal models are widely used to study the pathogenesis of many human diseases. However, there is no suitable experimental animal model that can completely simulate the clinical manifestations of COVID-19 patients to clarify COVID- 19 pathogenesis. Therefore, it is very important to establish and screen suitable animal models for COVID-19 research. This review summarizes the research status of COVID-19 animal models, compares the advantages and shortcomings of different animal models in COVID-19 basic research, and reviews the latest research progress and prospects of different types of COVID-19 animal model. The findings may provide a reference for the further development of animal models for the post- COVID-19 era.