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动物模型与实验医学（英文）
中国实验动物学会、中国医学科学院医学实验动物研究所
动物模型与实验医学（英文）

中国实验动物学会、中国医学科学院医学实验动物研究所

季刊

2096-5451

动物模型与实验医学（英文）/Journal Animal Models and Experimental MedicineCSCD北大核心
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    Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation

    Ruqiang YuanLei QianHu XuWeijing Yun...
    397-407页
    查看更多>>摘要：Background:Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health.Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis.Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypoten-sive effect.This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L.(CuECs) and cucurbitacin B (CuB) on restenosis.Methods:C57BL/6 mice were subjected to left carotid artery ligation and subcu-taneously injected with CuECs or CuB for 4 weeks.Hematoxylin-Eosin,immuno-fluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia.Western blot,real-time PCR,flow cytometry analysis,EdU staining and cellular immunofluorescence assay were em-ployed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro.The potential interactions of CuECs with cyclin A2 were performed by molecular docking.Results:The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells.Furthermore,CuECs and CuB mediated cell cycle arrest at the S phase.Autodocking analysis demonstrated that CuB,CuD,CuE and CuI had high binding en-ergy for cyclin A2.Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression.Moreover,the expression of cyclin A2 in CuEC-and CuB-treated neointima was downregulated.Conclusions:CuECs,especially CuB,exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.
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    • 维普

    MiR-106a targets ATG7 to inhibit autophagy and angiogenesis after myocardial infarction

    Guofeng BaiJinghao YangWeili LiaoXiaofeng Zhou...
    408-418页
    查看更多>>摘要：Background:Myocardial infarction (MI) is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in MI.But the specific mechanism remains unknown.In this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis.Methods:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells.Then we identified ATG7,which was the down-stream target gene of miR-106a .The expression of miR-106a and ATG7 was investi-gated in the rat model of MI.Results:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial cells.Moreover,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a .The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas.Conclusion:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7 .This mechanism may be a potential therapeutic treatment for MI.
      原文链接:
    • 万方数据
    • 维普

    Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs

    Yunxiao JiaYuqiong ZhaoMiaomiao NiuChangqi Zhao...
    419-432页
    查看更多>>摘要：Background:To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group (n=3) and a non-susceptible group ( n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.
      原文链接:
    • 万方数据
    • 维普

    Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus

    Xin-Yue LiuHan-Wen ZhengFeng-Zhong WangTul-Wahab Atia...
    433-443页
    查看更多>>摘要：In traditional Chinese medicine (TCM),based on various pathogenic symptoms and the'golden chamber'medical text,Huangdi Neijing,diabetes mellitus falls under the category'collateral disease'.TCM,with its wealth of experience,has been treating diabetes for over two millennia.Different antidiabetic Chinese herbal medicines re-duce blood sugar,with their effective ingredients exerting unique advantages.As well as a glucose lowering effect,TCM also regulates bodily functions to prevent diabetes associated complications,with reduced side effects compared to western synthetic drugs.Chinese herbal medicine is usually composed of polysaccharides,saponins,al-kaloids,flavonoids,and terpenoids.These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion,enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals.These actions regulate glycolipid metabolism in the body,eventually achiev-ing the goal of normalizing blood glucose.Using different animal models,a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer.Nonetheless,there is a dearth of scientific data about the pharmacology,dose-effect relationship,and structure-activity relationship of TCM and its constituents.Further research into the efficacy,toxicity and mode of action of TCM,using different metabolic and molecular markers,is key to developing novel TCM antidiabetic formulations.
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    Uncovering the impact of alcohol on internal organs and reproductive health:Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways

    Eason Qi Zheng KongVetriselvan SubramaniyanNatasha Sura Anak Lubau
    444-459页
    查看更多>>摘要：This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4 (TLR4)/Nuclear factor kappa light chain enhancer of activated B cells (NF-kB) pathway and the Cytochrome P4502E1 (CYP2E1)/reactive oxygen spe-cies (ROS)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathways.The TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to al-cohol.Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns (PAMPs),leading to liver cell infection and subsequent inflammation.Concurrently,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid (DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant re-sponses.Excessive alcohol intake results in elevated liver enzymes (ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and lungs.Moreover,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and women.These findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.
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    • 维普

    Against all odds:The road to success in the development of human immune reconstitution mice

    Yixiao BinJing RenHaowei ZhangTianjiao Zhang...
    460-470页
    查看更多>>摘要：The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.
      原文链接:
    • 万方数据
    • 维普

    Animal models of tendon calcification:Past,present,and future

    Ruichen LiCanhao LaiHong LuoYujian Lan...
    471-483页
    查看更多>>摘要：Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery,or as an expression of fibrodysplasia ossificans progressiva.This condition can be referred to by various names in clinical practice and literature,including tendon ossification,tendon mineralization,heterotopic ossification,and calcific tendonitis.The exact pathogenesis of tendon calcification remains uncertain,but current mainstream research suggests that calcification is mostly cell mediated.To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process,selecting appropriate experimental animal models is important.Numerous animal models have been utilized in various clinical studies,each with its own set of advantages and limitations.In this review,we have discussed the advancements made in research on animal models of tendon calcification,with a focus on the selection of experimental animals,the sites of injury in these models,and the methods employed for modeling.
      原文链接:
    • 万方数据
    • 维普

    How can we establish animal models of HIV-associated lymphoma?

    Qing XiaoLiuyue ZhaiXiaomei ZhangYi Liu...
    484-496页
    查看更多>>摘要：Human immunodeficiency virus (HIV) infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma (HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.
      原文链接:
    • 万方数据
    • 维普

    Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical,molecular,and computational studie

    A.M.Abu AhmedMd.Atiar RahmanFarjana SharmenA.S.M.Ali Reza...
    497-522页
    查看更多>>摘要：Background:Many kinds of orchids have significant health benefits although ade-quate research on their biological functions is yet to be carried out.This study inves-tigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE).Methods:The protective effects of AODE were studied by analyzing its effect on liver function parameters,messenger RNA (mRNA) expression,and tissue histopatho-logical architecture.The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.Results:AODE significantly ( p<0.05) minimized the dose-dependent increase in acid phosphatase,aspartate aminotransferase,alanine aminotransferase,alkaline phos-phatase,γ-glutamyl transferase,lactate dehydrogenase,and total bilirubin compared to the reference drug silymarin.Malondialdehyde level decreased,and the antioxidant genes catalase ( CAT ),superoxide dismutase ( SOD ),β-actin,paraoxonase-1 ( PON1 ),and phosphofructokinase-1 ( PFK-1 ) were upregulated in AODE-treated paracetamol-intoxicated rats.A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS).The online toxicity assessment using SwissADME and admetSAR exhibited drug-like,nontoxic,and potential pharmaco-logical properties.Additionally,in silico analysis showed that isoacteoside,one of the identified compounds,exhibited the best docking score (-11.42) with the liver pro-tein human pituitary adenylate cyclase-1 (Protein Data Bank ID:3N94).Furthermore,network pharmacology analysis identified the top 10 hub genes,namely AKT1 (protein kinase B),CTNNB1 (catenin beta-1),SRC (proto-oncogene c-Src),TNF (tumor necrosis factor),EGFR (epidermal growth factor receptor),HSP90AA1 ( heat shock protein 90α ),MAPK3 (mitogen-activated protein kinase 3),STAT3 (signal transducer and activator of transcription 3),CASP3 (caspase protein),and ESR1 (estrogen receptor 1),which are responsible for hepatoprotective activity.Conclusion:The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.
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    A novel mouse model of calcific aortic valve stenosis

    Ningjing QianYaping WangWangxing HuNaifang Cao...
    523-532页
    查看更多>>摘要：Background:Calcific aortic valve stenosis (CAVS) is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposi-tion.Here,we aim to establish a mouse model to mimic the development and features of CAVS.Methods:The model was established via aortic valve wire injury (AVWI) combined with vitamin D subcutaneous injected in wild type C57/BL6 mice.Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradi-ent.Histopathological specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and inflammation.Results:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 days.Compared with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 days.In addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid model.Conclusions:We established a novel mouse model of CAVS that could be induced efficiently,robustly and economically,and without genetic intervention.It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effec-tive pharmacological targets.
      原文链接:
    • 万方数据
    • 维普