树鼩在生物医学研究中的优势与挑战
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摘要
动物模型是研究人类疾病发生机制和药物筛选及有效性和安全性评价的重要手段。随着分子生物学技术的发展及对疾病分子遗传机制研究的深入,啮齿类动物与人类遗传背景、生理及代谢特征等方面的差异使得啮齿类动物很难体现人类疾病的复杂症状,在生命科学研究中的局限性日益突出。灵长类动物在进化上与人类更为接近,其生物学特性与人类非常相似,在生命科学研究中有着不可替代的作用,但目前灵长类动物遗传操作困难、研究周期长、成本高。树鼩是一种在进化上比啮齿类更为接近灵长类的小型哺乳动物,其神经功能障碍和感染性疾病等多个系统的关键因子和信号通路与人有保守和独特的特征,同时与灵长类动物比较,具有易饲养、繁殖快、研究成本低等优点,目前已越来越多地应用于生物医学研究领域。本文基于树鼩在生理代谢过程和组织解剖结构方面的特点,分析其在生物医学研究中的优势与面临的问题。
Animal model is an important method to study the mechanism of human disease, to screen drug, and to evaluate the safety and efficacy of drugs. With the development of molecular biology technology and the study of molecular genetic mechanism of human diseases, it is difficult to study the complex symptoms of human diseases in biomedical research using rodents as a result of the differences in genetic background, physiological and metabolic characteristics between rodent and human, the limitation of rodent in life science research is increasingly prominent. Primates play an irreplaceable role in biomedical research due to its evolution and biological characteristics. However, the limitation of genetic manipulation, long breeding cycle and high cost restrict the application of primates in biomedical research.The evolution of tree shrews are more closer to the primate than rodents. Tree shrews has been increasingly applied in the field of biomedical research since its characteristics of easy breeding, fast reproduction,the low cost and the key factors of neurological dysfunction and infectious diseases are conservative compared with primates. Based on the characteristics of physiological metabolic process and anatomical structure of tree shrews, this paper analyzes the advantages and problems of tree shrew in biomedical research.
Animal model is an important method to study the mechanism of human disease, to screen drug, and to evaluate the safety and efficacy of drugs. With the development of molecular biology technology and the study of molecular genetic mechanism of human diseases, it is difficult to study the complex symptoms of human diseases in biomedical research using rodents as a result of the differences in genetic background, physiological and metabolic characteristics between rodent and human, the limitation of rodent in life science research is increasingly prominent. Primates play an irreplaceable role in biomedical research due to its evolution and biological characteristics. However, the limitation of genetic manipulation, long breeding cycle and high cost restrict the application of primates in biomedical research.The evolution of tree shrews are more closer to the primate than rodents. Tree shrews has been increasingly applied in the field of biomedical research since its characteristics of easy breeding, fast reproduction,the low cost and the key factors of neurological dysfunction and infectious diseases are conservative compared with primates. Based on the characteristics of physiological metabolic process and anatomical structure of tree shrews, this paper analyzes the advantages and problems of tree shrew in biomedical research.
引文
[1]Fan Y,Huang ZY,Cao CC,et al.Genome of the Chinese tree shrew[J].Nat Commun,2013,4(1):1426-1435.
[2]Yan H,Zhong G,Xu G,et al.Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis Band D virus[J].Elife,2012,1:e00049.
[3]Ding R,Zhang H,Zhang L,et al.Assessment of sequence homology and immunologic cross-reactivity between tree shrew(Tupaia belangeri)and human IL-21[J].PLoS One,2017,12(5):e0176707.
[4]Luo MT,Fan Y,Mu D,et al.Molecular cloning and characterization of APOBEC3 family in tree shrew[J].Gene,2018,646:143-152.
[5]Ruan P,Yang C,Su J,et al.Histopathological changes in the liver of tree shrew(Tupaia ngeri chinensis)persistently infected with hepatitis B virus[J].Virol J,2013,10:333.
[6]Yang C,Ruan P,Ou C,et al.Chronic hepatitis B virus infection and occurrence of hepatocellular carcinoma in tree shrews(Tupaia belangeri chinensis)[J].Virol J,2015,12:26.
[7]Feng Y,Feng YM,Feng Y,et al.Identification and characterization of liver microRNAs of the Chinese tree shrew via deep sequencing[J].Hepat Mon,2015,15(10):e29053.
[8]Feng Y,Feng YM,Lu C,et al.Tree shrew,a potential animal model for hepatitis C,supports the infection and replication of HCV in vitro and in vivo[J].J Gen Virol,2017,98(8):2069-2078.
[9]Foelix RF,Kretz R,Rager G.Structure and postnatal development of photoreceptors and their synapses in the retina of the tree shrew[J].Cell Tissue Res,1987,247(2):287-97.
[10]Muller B,Peichl L.Topography of cones and rods in the tree shrew retina[J].J Comp Neurol,1989,282:581-594.
[11]Levy AM,Fazio MA,Grytz R,et al.Experimental myopia increases and scleral crosslinking using genipin inhibits cyclic softening in the tree shrew sclera[J].Ophthalmic Physiol Opt,2018,38(3):246-256.
[12]Grytz R,El Hamdaoui M.Multi-scale modeling of visionguided remodeling and age-dependent growth of the rree shrew sclera during eye development and lens-induced myopia[J].J Elast,2017,129(1-2):171-195.
[13]Guo L,Frost MR,Siegwart JT Jr,et al.Scleral gene expression during recovery from myopia compared with expression during myopia development in tree shrew[J].Mol Vis,2014,20:1643-1659.
[14]He L,Frost MR,Siegwart JT Jr,et al.Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery[J].Exp Eye Res,2014,123:56-71.
[15]Liu HH,Kenning MS,Jobling AI,et al.Reduced scleral TIMP-2 expression is associated with myopia development:TIMP-2 supplementation stabilizes scleral biomarkers of myopia and limits myopia development[J].Invest Ophthalmol Vis Sci,2017,58(4):1971-1981.
[16]李丽红.单纯疱疹病毒潜伏感染树鼩模型的建立及其鉴定[D].长春:吉林大学,2015.
[17]李妍,李丽红,刘海,等.树鼩茄病镰刀菌性角膜炎房水中Th1/Th2炎性因子的变化[J].眼科新进展,2017,37(9):824-827.
[18]Samuels BC,Siegwart JT,Zhan W,et al.A novel tree shrew(Tupaia belangeri)model of glaucoma[J].Invest Ophthalmol Vis Sci,2018,59(7):3136-3143.
[19]Lu JS,Yue F,Liu X,et al.Characterization of the anterior cingulate cortex in adult tree shrew[J].Mol Pain,2016,12:1744806916684515.
[20]祁可可,冯敏,孟肖路,等.树鼩的社会挫败抑郁模型[J].心理科学进展,2012,20:1787-1793.
[21]Fang H,Sun YJ,Lv YH,et al.High activity of the stress promoter contributes to susceptibility to stress in the tree shrew[J].Sci Rep,2016,6:24905.
[22]Schmelting B,Corbach-S?hle S,Kohlhause S,et al.Agomelatine in the tree shrew model of depression:effects on stress-induced nocturnal hyperthermia and hormonalstatus[J].Eur Neuropsychopharmacol,2014,24(3):437-447.
[23]Wang J,Chai AP,Zhou QX,et al.Chronic clomipramine treatment reverses core symptom of depression in subordinate tree shrews[J].PLoS One,2013,8(12):e80980.
[24]Pawlik M,Fuchs E,Walker LC,et al.Primate-like amyloidb sequence but no cerebral amyloidosis in aged tree shrews[J].Neurobiol Aging,1999,20(1):47-51.
[25]Yamashita A,Fuchs E,Taira M,et al.Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques[J].J Med Primatol,2012,41(3):147-157.
[26]何保丽,角建林,李波,等.天麻素对老年痴呆树鼩海马BDNF表达的影响[J].昆明医科大学学报,2013,34(9):29-30.
[27]Lin N,Xiong LL,Zhang RP,et al.Erratum to:injection of Ab1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew[J].Apoptosis,2016,21(5):641.
[28]Hofmann W,M?ller P,Schwaier A,et al.Malignant tumours in Tupaia(tree shrew)[J].J Med Primatol,1981,10(2-3):155-163.
[29]Elliot OS,Elliot MW,Lisco H.Breast cancer in a tree shrew(Tupaia glis)[J].Nature,1966,211(5053):1105.
[30]Brack M,Schwartz P,Heinrichs T,et al.Tumors of the respiratory tract observed at the German Primate Center,1978-1994[J].J Med Primatol,1996,25(6):424-434.
[31]Tong Y,Hao J,Tu Q,et al.A tree shrew glioblastoma model recapitulates features of human glioblastoma[J].Oncotarget,2017,8(11):17897-17907.
[32]Xia HJ,He BL,Wang CY,et al.PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews[J].Eur J Cancer,2014,50(18):3230-3242.
[33]Shao M,Ge GZ,Liu WJ,et al.Characterization and phylogenetic analysis of Kruppel-like transcription factor(KLF)gene family in tree shrews(Tupaia belangeri chinensis)[J].Oncotarget,2017,7(10):16325-16339.
[34]Su JJ,Ban KC,Li Y,et al.Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews[J].World JGastroenterol,2004,10(24):3559-3563.
[35]Ye L,He M,Huang Y,et al.Tree shrew as a new animal model for the study of lung cancer[J].Oncol Lett,2016,11(3):2091-2095.
[36]Zhao F,Guo X,Wang Y,et al.Drug target mining and analysis of the Chinese tree shrew for pharmacological testing[J].PLoS One,2014,9(8):e104191.
[37]Wang J,Xu XL,Ding ZY,et al.Basal physiological parameters in domesticated tree shrews(Tupaia belangeri chinensis)[J].Zoological Research,2013,34(2):176-181.
[38]Rabb GB,Getty RE,Williamson WM,et al.Spontaneous diabetes mellitus in tree shrews,Urogale everetti[J].Diabetes,1966,15(5):327-330.
[39]冼苏,黄松,秦映芬,等.链脲佐菌素诱导树鼩糖尿病动物模型研究[J].广西医科大学学报,2000(6):945-948.
[40]吴晓云,李昀海,常青,等.链脲佐菌素诱导树鼩2型糖尿病[J].动物学研究,2013,34(2):108-115.
[41]Pan XH,Huang X,Ruan GP,et al.Umbilical cord mesenchymal stem cells are able to undergo differentiation into functional islet-like cells in type 2 diabetic tree shrews[J].Mol Cell Probes,2017,34:1-12.
[42]Pan XH,Zhu L,Yao X,et al.Development of a tree shrew metabolic syndrome model and use of umbilical cord mesenchymal stem cell transplantation for treatment[J].Cytotechnology,2016,68(6):2449-2467.
[43]Zhang LQ,Zhang ZG,Li YH,et al.Cholesterol induces lipoprotein lipase expression in a tree shrew(Tupaia belangeri chinensis)model of non-alcoholic fatty liver disease[J].Scientific Reports,2015,5:15970.
[44]Xing H,Jia K,He J,et al.Establishment of the tree shrew as an alcohol-induced fatty liver model for the study of alcoholic liver diseases[J].PLoS One,2015,10(6):e0128253.
[2]Yan H,Zhong G,Xu G,et al.Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis Band D virus[J].Elife,2012,1:e00049.
[3]Ding R,Zhang H,Zhang L,et al.Assessment of sequence homology and immunologic cross-reactivity between tree shrew(Tupaia belangeri)and human IL-21[J].PLoS One,2017,12(5):e0176707.
[4]Luo MT,Fan Y,Mu D,et al.Molecular cloning and characterization of APOBEC3 family in tree shrew[J].Gene,2018,646:143-152.
[5]Ruan P,Yang C,Su J,et al.Histopathological changes in the liver of tree shrew(Tupaia ngeri chinensis)persistently infected with hepatitis B virus[J].Virol J,2013,10:333.
[6]Yang C,Ruan P,Ou C,et al.Chronic hepatitis B virus infection and occurrence of hepatocellular carcinoma in tree shrews(Tupaia belangeri chinensis)[J].Virol J,2015,12:26.
[7]Feng Y,Feng YM,Feng Y,et al.Identification and characterization of liver microRNAs of the Chinese tree shrew via deep sequencing[J].Hepat Mon,2015,15(10):e29053.
[8]Feng Y,Feng YM,Lu C,et al.Tree shrew,a potential animal model for hepatitis C,supports the infection and replication of HCV in vitro and in vivo[J].J Gen Virol,2017,98(8):2069-2078.
[9]Foelix RF,Kretz R,Rager G.Structure and postnatal development of photoreceptors and their synapses in the retina of the tree shrew[J].Cell Tissue Res,1987,247(2):287-97.
[10]Muller B,Peichl L.Topography of cones and rods in the tree shrew retina[J].J Comp Neurol,1989,282:581-594.
[11]Levy AM,Fazio MA,Grytz R,et al.Experimental myopia increases and scleral crosslinking using genipin inhibits cyclic softening in the tree shrew sclera[J].Ophthalmic Physiol Opt,2018,38(3):246-256.
[12]Grytz R,El Hamdaoui M.Multi-scale modeling of visionguided remodeling and age-dependent growth of the rree shrew sclera during eye development and lens-induced myopia[J].J Elast,2017,129(1-2):171-195.
[13]Guo L,Frost MR,Siegwart JT Jr,et al.Scleral gene expression during recovery from myopia compared with expression during myopia development in tree shrew[J].Mol Vis,2014,20:1643-1659.
[14]He L,Frost MR,Siegwart JT Jr,et al.Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery[J].Exp Eye Res,2014,123:56-71.
[15]Liu HH,Kenning MS,Jobling AI,et al.Reduced scleral TIMP-2 expression is associated with myopia development:TIMP-2 supplementation stabilizes scleral biomarkers of myopia and limits myopia development[J].Invest Ophthalmol Vis Sci,2017,58(4):1971-1981.
[16]李丽红.单纯疱疹病毒潜伏感染树鼩模型的建立及其鉴定[D].长春:吉林大学,2015.
[17]李妍,李丽红,刘海,等.树鼩茄病镰刀菌性角膜炎房水中Th1/Th2炎性因子的变化[J].眼科新进展,2017,37(9):824-827.
[18]Samuels BC,Siegwart JT,Zhan W,et al.A novel tree shrew(Tupaia belangeri)model of glaucoma[J].Invest Ophthalmol Vis Sci,2018,59(7):3136-3143.
[19]Lu JS,Yue F,Liu X,et al.Characterization of the anterior cingulate cortex in adult tree shrew[J].Mol Pain,2016,12:1744806916684515.
[20]祁可可,冯敏,孟肖路,等.树鼩的社会挫败抑郁模型[J].心理科学进展,2012,20:1787-1793.
[21]Fang H,Sun YJ,Lv YH,et al.High activity of the stress promoter contributes to susceptibility to stress in the tree shrew[J].Sci Rep,2016,6:24905.
[22]Schmelting B,Corbach-S?hle S,Kohlhause S,et al.Agomelatine in the tree shrew model of depression:effects on stress-induced nocturnal hyperthermia and hormonalstatus[J].Eur Neuropsychopharmacol,2014,24(3):437-447.
[23]Wang J,Chai AP,Zhou QX,et al.Chronic clomipramine treatment reverses core symptom of depression in subordinate tree shrews[J].PLoS One,2013,8(12):e80980.
[24]Pawlik M,Fuchs E,Walker LC,et al.Primate-like amyloidb sequence but no cerebral amyloidosis in aged tree shrews[J].Neurobiol Aging,1999,20(1):47-51.
[25]Yamashita A,Fuchs E,Taira M,et al.Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques[J].J Med Primatol,2012,41(3):147-157.
[26]何保丽,角建林,李波,等.天麻素对老年痴呆树鼩海马BDNF表达的影响[J].昆明医科大学学报,2013,34(9):29-30.
[27]Lin N,Xiong LL,Zhang RP,et al.Erratum to:injection of Ab1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew[J].Apoptosis,2016,21(5):641.
[28]Hofmann W,M?ller P,Schwaier A,et al.Malignant tumours in Tupaia(tree shrew)[J].J Med Primatol,1981,10(2-3):155-163.
[29]Elliot OS,Elliot MW,Lisco H.Breast cancer in a tree shrew(Tupaia glis)[J].Nature,1966,211(5053):1105.
[30]Brack M,Schwartz P,Heinrichs T,et al.Tumors of the respiratory tract observed at the German Primate Center,1978-1994[J].J Med Primatol,1996,25(6):424-434.
[31]Tong Y,Hao J,Tu Q,et al.A tree shrew glioblastoma model recapitulates features of human glioblastoma[J].Oncotarget,2017,8(11):17897-17907.
[32]Xia HJ,He BL,Wang CY,et al.PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews[J].Eur J Cancer,2014,50(18):3230-3242.
[33]Shao M,Ge GZ,Liu WJ,et al.Characterization and phylogenetic analysis of Kruppel-like transcription factor(KLF)gene family in tree shrews(Tupaia belangeri chinensis)[J].Oncotarget,2017,7(10):16325-16339.
[34]Su JJ,Ban KC,Li Y,et al.Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews[J].World JGastroenterol,2004,10(24):3559-3563.
[35]Ye L,He M,Huang Y,et al.Tree shrew as a new animal model for the study of lung cancer[J].Oncol Lett,2016,11(3):2091-2095.
[36]Zhao F,Guo X,Wang Y,et al.Drug target mining and analysis of the Chinese tree shrew for pharmacological testing[J].PLoS One,2014,9(8):e104191.
[37]Wang J,Xu XL,Ding ZY,et al.Basal physiological parameters in domesticated tree shrews(Tupaia belangeri chinensis)[J].Zoological Research,2013,34(2):176-181.
[38]Rabb GB,Getty RE,Williamson WM,et al.Spontaneous diabetes mellitus in tree shrews,Urogale everetti[J].Diabetes,1966,15(5):327-330.
[39]冼苏,黄松,秦映芬,等.链脲佐菌素诱导树鼩糖尿病动物模型研究[J].广西医科大学学报,2000(6):945-948.
[40]吴晓云,李昀海,常青,等.链脲佐菌素诱导树鼩2型糖尿病[J].动物学研究,2013,34(2):108-115.
[41]Pan XH,Huang X,Ruan GP,et al.Umbilical cord mesenchymal stem cells are able to undergo differentiation into functional islet-like cells in type 2 diabetic tree shrews[J].Mol Cell Probes,2017,34:1-12.
[42]Pan XH,Zhu L,Yao X,et al.Development of a tree shrew metabolic syndrome model and use of umbilical cord mesenchymal stem cell transplantation for treatment[J].Cytotechnology,2016,68(6):2449-2467.
[43]Zhang LQ,Zhang ZG,Li YH,et al.Cholesterol induces lipoprotein lipase expression in a tree shrew(Tupaia belangeri chinensis)model of non-alcoholic fatty liver disease[J].Scientific Reports,2015,5:15970.
[44]Xing H,Jia K,He J,et al.Establishment of the tree shrew as an alcohol-induced fatty liver model for the study of alcoholic liver diseases[J].PLoS One,2015,10(6):e0128253.