我国实验小型猪的发展现状及展望
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摘要
实验动物广泛应用于科学研究领域,实验小型猪在医学研究领域中越来越得到重视。中国小型猪种源丰富,不同种群各具特色,遗传性状稳定。近年来中国实验小型猪的研究处于快速发展阶段,生产和使用均在逐年增加。我国发展实验小型猪具有天然封闭群特性和高度近交等得天独厚的条件,品系化、标准化、规模化和产业化是我国实验用小型猪的主要发展趋势。我国实验用小型猪发展当前面临的问题主要表现在:保护力度小、发展阻力大、育成品系少三个方面。育成中国各具特色的实验用小型猪品系需要增加投入,利用先进的科学技术例如基因编辑和动物克隆技术,加速小型猪的定向化培育进程。
Laboratory Animals are widely used in scientific research, and experimental miniature swine are getting more and more attention in the field of medical research around the world. In China, the resources of miniature swine are very rich, different species have their own characteristics and their genetic characters are stable. In recent years, the research on experimental miniature swine is in a rapid development stage in China, and the production and usage are increasing year by year. The development of experimental miniature swine in China has the unique advantages of natural closed group characteristics and high inbreeding. The main development trend of experimental miniature swine in China is strain-systematization, standardization, large-scale and industrialization. The current problems faced by the development of experimental miniature swine in China are mainly reflected in three aspects: weak protection, considerable resistance to development, and few of finished strains. Breeding the strain of experimental miniature swine with different characteristics in China requires an increase in investment, using advanced science and technology such as gene editing and animal cloning technology to accelerate the process of orientational breeding of miniature swine.
Laboratory Animals are widely used in scientific research, and experimental miniature swine are getting more and more attention in the field of medical research around the world. In China, the resources of miniature swine are very rich, different species have their own characteristics and their genetic characters are stable. In recent years, the research on experimental miniature swine is in a rapid development stage in China, and the production and usage are increasing year by year. The development of experimental miniature swine in China has the unique advantages of natural closed group characteristics and high inbreeding. The main development trend of experimental miniature swine in China is strain-systematization, standardization, large-scale and industrialization. The current problems faced by the development of experimental miniature swine in China are mainly reflected in three aspects: weak protection, considerable resistance to development, and few of finished strains. Breeding the strain of experimental miniature swine with different characteristics in China requires an increase in investment, using advanced science and technology such as gene editing and animal cloning technology to accelerate the process of orientational breeding of miniature swine.
引文
[1] 邹移海,徐志伟,黄韧,等.实验动物学[M].第2版.北京:科学出版社,2012.Zou YH, Xu ZW, Huang R, et al. Laboratory Animal Science [M]. 2nd ed. Beijing: Science Press, 2012.
[2] Tikhonov VN, Bobovich VE. Genetics and major applications of supersmall mini pigs in medicine and biotechnology [J]. Russian J Genet Appl Res, 2012, 2(1): 97-104.
[3] 国家科技基础条件平台中心.中国实验动物资源调查与发展趋势[M].北京:科学出版社,2017.National Science & Technology Infrastructure Center. Survey and development trend of animal resources in China[M]. Beijing: Science Press, 2017.
[4] 王桂花,尹晓敏,孙霞,等.国内外小型猪资源概况[J].中国比较医学杂志,2009(02):71-73.Wang GH, Yin XM, Sun X, et al. General situation of miniature pig resources at home and abroad [J]. Chin J Comp Med, 2009(02): 71-73.
[5] Kobayshi E, Hanazono Y, Kunita S. Swine used in the medical university: overview of 20 years of experience [J]. Exp Anim, 2018, 67(1): 7-13.
[6] 张贺,王承利,王洋,等.小型猪动物模型在医学领域中的研究应用 [J].中国畜牧兽医,2012(07):263-266.Zhang H, Wang CL, Wang Y, et al. Progress and application of miniature pig models on medical domain [J]. Chin Anim Husbandry Vet Med, 2012(07): 263-266.
[7] Dexter JD, Tumbleson ME, Hutcheson DP, et al. Sinclair(S-1) miniature swine as a model for the study of human alcoholism [J]. Ann N Y Acad Sci, 2010, 273(1):188-193.
[8] Cevallos WH, Holmes WL, Myers RN, et al. Swine in atherosclerosis research-development of an experimental animal model and study of the effect of dietary fats on cholesterol metabolism [J]. Atherosclerosis, 1979, 34(3): 303-317.
[9] Phillips RW, Panepinto LM, Will DH, et al. The effects of alloxan diabetes on Yucatan miniature swine and their progeny [J]. Metabolism, 1980, 29(1): 40-45.
[10] Foubert P, Doyle-Eisele M, Gonzalez A, et al. Development of a combined radiation and full thickness burn injury minipig model to study the effects of uncultured adipose-derived regenerative cell therapy in wound healing [J]. Int J Radiat Biol, 2016, 93(3): 340-350.
[11] 唐颜苹,张癸荣,聂凌云,等.农大Ⅲ系实验小型猪烧伤模型的建立 [J].解放军药学学报,2015, 31 (6): 538-541.Tang YP, Zhang GR, Nie LY, et al. Establishment of burn model using Nongda III miniature pigs [J]. Pharm J Chin PLA, 2015, 31(06): 538-541.
[12] Navarro-Alvarez N, Gon?alves BMM, Andrews AR, et al. A CFA-Induced model of inflammatory skin disease in miniature swine [J]. Int J Inflam, 2018, 2018: 6916920.
[13] Jimi S, Matsumura H. Effect of chymase activity on skin thickness in the clawn miniature pig hypertrophic scarring model [J]. J Plast Surg Hand Surg, 2017, 51(6): 446-452.
[14] 吴垒,魏嘉,华修国,等.基于高脂饲料饲喂及球囊拉伤技术的小型猪颈总动脉粥样硬化模型构建[J]. 上海交通大学学报(农业科学版), 2018,36(1):20-23.Wu L, Wei J, Hua XG, et al. Establishment of carotid atherosclerosis model in miniature pig based on high fat diet and balloon strain technique [J]. J Shanghai Jiaotong Univ (Agric Sci), 2018, 36(1): 20-23.
[15] Zhao Y, Xiang L, Liu Y, et al. Atherosclerosis induced by a high-cholesterol and high-fat diet in the inbred strain of the Wuzhishan miniature pig [J]. Anim Biotechnol, 2017, 29(2): 110-118.
[16] Li W, Chen X, Riley AM, et al. Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs [J]. Basic Res Cardiol, 2017, 112(5): 54.
[17] Amuzie C, Swart JR, Rogers CS, et al. A translational model for diet-related atherosclerosis: Effect of statins on hypercholesterolemia and atherosclerosis in a minipig [J]. Toxicol Pathol, 2016, 44(3): 442-449.
[18] 刘亚千,赵玉琼,王凯,等.巴马小型猪1型糖尿病模型的建立 [J].实验动物科学,2015, 32(04):1-7.Liu YQ, Zhao YQ, Wang K, et al. Establishment of type 1 diabetes mellitus model in Bama minipig [J]. Lab Anim Sci, 2015, 32(04): 1-7.
[19] 吴延军,夏攀洁,严雪瑜,等.高脂高糖饲料联合低剂量链脲佐菌素(STZ)诱导广西巴马小型猪2型糖尿病动物模型的建立[J].基因组学与应用生物学,2017, 36(06):2393-2398.Wu YJ, Xia PJ, Yan XY, et al. Combination of high fat/high carbohydrates diet and low-dose streptozotocin-(STZ) induced a model for type 2 diabetes in Guangxi Bama mini-pig [J]. Genom Appl Biol, 2017(06): 2393-2398.
[20] 李松,房殿吉,王占义,等.小型猪下颌骨放射性骨坏死动物模型的建立[J].华西口腔医学杂志,2015, 33(06):570-574.Li S, Fang DJ, Wang ZY, et al. Establishment of a miniature pig model of mandibular osteoradionecrosis [J]. West Chin J Stomatol, 2015, 33(06): 570-574.
[21] Christensen BB, Foldager CB, Olesen ML, et al. Experimental articular cartilage repair in the G?ttingen minipig: the influence of multiple defects per knee [J]. J Exp Orthop, 2015, 2(1): 13.
[22] 许俊,刚蔷蔷,郝鹏,等.西藏小型猪缺氧缺血性脑病模型的建立及病理和影像学表现[J].南方医科大学学报,2016,36(5):705-709.Xu J, Gang QQ, Hao P, et al. Pathological and magnetic resonance imaging findings in a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy [J]. J Southern Med Univ, 2016, 36(5): 705-709.
[23] Baxa M, Hruskaplochan M, Juhsa S, et al. A transgenic minipig models of Huntington’s disease [J]. J Huntington′s Dis, 2013, 2(1): 47-68.
[24] 张一鸣,李晓蕾,李欣然,等.氯胺酮对小型猪不同脑区氨基酸类神经递质的影响[J].中国兽医杂志,2018, 54(01):3-7.Zhang YM, Li XL, Li XR, et al. Effects of Ketamine on amino acid neurotransmitter in different encephalic regions of miniature pigs [J]. Chin J Vet Med, 2018, 54(01): 3-7.
[25] 郭岑,李欣然,李晓蕾,等.咪达唑仑对小型猪不同脑区氨基酸类神经递质的影响[J].中国兽医杂志,2017, 53(05):34-36.Guo C, Li XR, Li XL, et al. Effects of Midazolam on amino acid neurotransmitter in different encephalic regions of miniature pigs [J]. Chin J Vet Med, 2017, 53(05): 34-36.
[26] 赵世波,李彩霞,尹纪业.小型猪在药物安全性评价中的价值和应用 [J].中国新药杂志,2017,26(24):2952-2959.Zhao SB, Li CX, Yin JY. The value and application of minipig in nonclinical drug safety evaluation [J]. Chin J New Drug, 2017(24): 2952-2959.
[27] Manno RA, Grassetti A, Oberto G, et al. The minipig as a new model for the evaluation of doxorubicin-induced chronic toxicity [J]. J Appl Toxicol, 2015, 36(8): 1060-1072.
[28] Schuurman HJ. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-Chapter 2: Source pigs [J]. Xenotransplantation, 2009, 16(4): 215-222.
[29] Zhu HT, Liang Y, Lyu Y,et al.Optimal pig donor selection in islet xenotransplantation: Current status and future perspectives [J]. J Zhejiang Univ Sci B,2014, 15(08): 681-691.
[30] Sachs DH. Transplantation tolerance through mixed chimerism: From allo to xeno [J]. Xenotransplantation, 2018, 25(3): e12420.
[31] 蔡悦.实验动物保护的法律问题研究 [J].天津商务职业学院学报, 2015(02): 78-81.Cai Y. Legal research on laboratory animal protection [J]. J Tianjin Coll Com, 2015(02): 78-81.
[32] Riverae E, Hernandez R, Carissimi AS, et al. Laboratory animal legislation in Latin America [J]. ILAR J, 2016, 57(3): 293-300.
[33] 孙德明,李蔚鸥,王天奇,等.实验动物福利伦理审查的标准化与我国新国标解读[J].中国比较医学杂志,2018(10):133-137.Sun DM, Li WO, Wang TQ, et al. Standardization of ethical review for laboratory animal welfare and interpretation of the new national standards in China [J]. Chin J Comp Med, 2018(10): 133-137.
[34] 冯书堂,李奎,刘岚,等.小型猪近交系新品种的培育与开发利用[J].农业生物技术学报,2015, 23 (02): 274-280.Feng ST, Li K, Liu L, et al. Cultivation and application of miniature pig (Sus scrofa) inbred [J]. Chin J Agric Biotechnol, 2015, 23(02): 274-280.
[35] Amstislavsky SY, Brusentsev EY, Okotrub KA, et al. Embryo and gamete cryopreservation for genetic resources conservation of laboratory animals [J]. Ontogenez, 2015, 46(2): 67-81.
[36] Yang H, Wu Z. Genome editing of pigs for agriculture and biomedicine [J].Front Genet, 2018, 9: 360.
[37] Niu D, Wei HJ, Lin L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 [J]. Science, 2017, 357(6357): 1303-1307.
[2] Tikhonov VN, Bobovich VE. Genetics and major applications of supersmall mini pigs in medicine and biotechnology [J]. Russian J Genet Appl Res, 2012, 2(1): 97-104.
[3] 国家科技基础条件平台中心.中国实验动物资源调查与发展趋势[M].北京:科学出版社,2017.National Science & Technology Infrastructure Center. Survey and development trend of animal resources in China[M]. Beijing: Science Press, 2017.
[4] 王桂花,尹晓敏,孙霞,等.国内外小型猪资源概况[J].中国比较医学杂志,2009(02):71-73.Wang GH, Yin XM, Sun X, et al. General situation of miniature pig resources at home and abroad [J]. Chin J Comp Med, 2009(02): 71-73.
[5] Kobayshi E, Hanazono Y, Kunita S. Swine used in the medical university: overview of 20 years of experience [J]. Exp Anim, 2018, 67(1): 7-13.
[6] 张贺,王承利,王洋,等.小型猪动物模型在医学领域中的研究应用 [J].中国畜牧兽医,2012(07):263-266.Zhang H, Wang CL, Wang Y, et al. Progress and application of miniature pig models on medical domain [J]. Chin Anim Husbandry Vet Med, 2012(07): 263-266.
[7] Dexter JD, Tumbleson ME, Hutcheson DP, et al. Sinclair(S-1) miniature swine as a model for the study of human alcoholism [J]. Ann N Y Acad Sci, 2010, 273(1):188-193.
[8] Cevallos WH, Holmes WL, Myers RN, et al. Swine in atherosclerosis research-development of an experimental animal model and study of the effect of dietary fats on cholesterol metabolism [J]. Atherosclerosis, 1979, 34(3): 303-317.
[9] Phillips RW, Panepinto LM, Will DH, et al. The effects of alloxan diabetes on Yucatan miniature swine and their progeny [J]. Metabolism, 1980, 29(1): 40-45.
[10] Foubert P, Doyle-Eisele M, Gonzalez A, et al. Development of a combined radiation and full thickness burn injury minipig model to study the effects of uncultured adipose-derived regenerative cell therapy in wound healing [J]. Int J Radiat Biol, 2016, 93(3): 340-350.
[11] 唐颜苹,张癸荣,聂凌云,等.农大Ⅲ系实验小型猪烧伤模型的建立 [J].解放军药学学报,2015, 31 (6): 538-541.Tang YP, Zhang GR, Nie LY, et al. Establishment of burn model using Nongda III miniature pigs [J]. Pharm J Chin PLA, 2015, 31(06): 538-541.
[12] Navarro-Alvarez N, Gon?alves BMM, Andrews AR, et al. A CFA-Induced model of inflammatory skin disease in miniature swine [J]. Int J Inflam, 2018, 2018: 6916920.
[13] Jimi S, Matsumura H. Effect of chymase activity on skin thickness in the clawn miniature pig hypertrophic scarring model [J]. J Plast Surg Hand Surg, 2017, 51(6): 446-452.
[14] 吴垒,魏嘉,华修国,等.基于高脂饲料饲喂及球囊拉伤技术的小型猪颈总动脉粥样硬化模型构建[J]. 上海交通大学学报(农业科学版), 2018,36(1):20-23.Wu L, Wei J, Hua XG, et al. Establishment of carotid atherosclerosis model in miniature pig based on high fat diet and balloon strain technique [J]. J Shanghai Jiaotong Univ (Agric Sci), 2018, 36(1): 20-23.
[15] Zhao Y, Xiang L, Liu Y, et al. Atherosclerosis induced by a high-cholesterol and high-fat diet in the inbred strain of the Wuzhishan miniature pig [J]. Anim Biotechnol, 2017, 29(2): 110-118.
[16] Li W, Chen X, Riley AM, et al. Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs [J]. Basic Res Cardiol, 2017, 112(5): 54.
[17] Amuzie C, Swart JR, Rogers CS, et al. A translational model for diet-related atherosclerosis: Effect of statins on hypercholesterolemia and atherosclerosis in a minipig [J]. Toxicol Pathol, 2016, 44(3): 442-449.
[18] 刘亚千,赵玉琼,王凯,等.巴马小型猪1型糖尿病模型的建立 [J].实验动物科学,2015, 32(04):1-7.Liu YQ, Zhao YQ, Wang K, et al. Establishment of type 1 diabetes mellitus model in Bama minipig [J]. Lab Anim Sci, 2015, 32(04): 1-7.
[19] 吴延军,夏攀洁,严雪瑜,等.高脂高糖饲料联合低剂量链脲佐菌素(STZ)诱导广西巴马小型猪2型糖尿病动物模型的建立[J].基因组学与应用生物学,2017, 36(06):2393-2398.Wu YJ, Xia PJ, Yan XY, et al. Combination of high fat/high carbohydrates diet and low-dose streptozotocin-(STZ) induced a model for type 2 diabetes in Guangxi Bama mini-pig [J]. Genom Appl Biol, 2017(06): 2393-2398.
[20] 李松,房殿吉,王占义,等.小型猪下颌骨放射性骨坏死动物模型的建立[J].华西口腔医学杂志,2015, 33(06):570-574.Li S, Fang DJ, Wang ZY, et al. Establishment of a miniature pig model of mandibular osteoradionecrosis [J]. West Chin J Stomatol, 2015, 33(06): 570-574.
[21] Christensen BB, Foldager CB, Olesen ML, et al. Experimental articular cartilage repair in the G?ttingen minipig: the influence of multiple defects per knee [J]. J Exp Orthop, 2015, 2(1): 13.
[22] 许俊,刚蔷蔷,郝鹏,等.西藏小型猪缺氧缺血性脑病模型的建立及病理和影像学表现[J].南方医科大学学报,2016,36(5):705-709.Xu J, Gang QQ, Hao P, et al. Pathological and magnetic resonance imaging findings in a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy [J]. J Southern Med Univ, 2016, 36(5): 705-709.
[23] Baxa M, Hruskaplochan M, Juhsa S, et al. A transgenic minipig models of Huntington’s disease [J]. J Huntington′s Dis, 2013, 2(1): 47-68.
[24] 张一鸣,李晓蕾,李欣然,等.氯胺酮对小型猪不同脑区氨基酸类神经递质的影响[J].中国兽医杂志,2018, 54(01):3-7.Zhang YM, Li XL, Li XR, et al. Effects of Ketamine on amino acid neurotransmitter in different encephalic regions of miniature pigs [J]. Chin J Vet Med, 2018, 54(01): 3-7.
[25] 郭岑,李欣然,李晓蕾,等.咪达唑仑对小型猪不同脑区氨基酸类神经递质的影响[J].中国兽医杂志,2017, 53(05):34-36.Guo C, Li XR, Li XL, et al. Effects of Midazolam on amino acid neurotransmitter in different encephalic regions of miniature pigs [J]. Chin J Vet Med, 2017, 53(05): 34-36.
[26] 赵世波,李彩霞,尹纪业.小型猪在药物安全性评价中的价值和应用 [J].中国新药杂志,2017,26(24):2952-2959.Zhao SB, Li CX, Yin JY. The value and application of minipig in nonclinical drug safety evaluation [J]. Chin J New Drug, 2017(24): 2952-2959.
[27] Manno RA, Grassetti A, Oberto G, et al. The minipig as a new model for the evaluation of doxorubicin-induced chronic toxicity [J]. J Appl Toxicol, 2015, 36(8): 1060-1072.
[28] Schuurman HJ. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-Chapter 2: Source pigs [J]. Xenotransplantation, 2009, 16(4): 215-222.
[29] Zhu HT, Liang Y, Lyu Y,et al.Optimal pig donor selection in islet xenotransplantation: Current status and future perspectives [J]. J Zhejiang Univ Sci B,2014, 15(08): 681-691.
[30] Sachs DH. Transplantation tolerance through mixed chimerism: From allo to xeno [J]. Xenotransplantation, 2018, 25(3): e12420.
[31] 蔡悦.实验动物保护的法律问题研究 [J].天津商务职业学院学报, 2015(02): 78-81.Cai Y. Legal research on laboratory animal protection [J]. J Tianjin Coll Com, 2015(02): 78-81.
[32] Riverae E, Hernandez R, Carissimi AS, et al. Laboratory animal legislation in Latin America [J]. ILAR J, 2016, 57(3): 293-300.
[33] 孙德明,李蔚鸥,王天奇,等.实验动物福利伦理审查的标准化与我国新国标解读[J].中国比较医学杂志,2018(10):133-137.Sun DM, Li WO, Wang TQ, et al. Standardization of ethical review for laboratory animal welfare and interpretation of the new national standards in China [J]. Chin J Comp Med, 2018(10): 133-137.
[34] 冯书堂,李奎,刘岚,等.小型猪近交系新品种的培育与开发利用[J].农业生物技术学报,2015, 23 (02): 274-280.Feng ST, Li K, Liu L, et al. Cultivation and application of miniature pig (Sus scrofa) inbred [J]. Chin J Agric Biotechnol, 2015, 23(02): 274-280.
[35] Amstislavsky SY, Brusentsev EY, Okotrub KA, et al. Embryo and gamete cryopreservation for genetic resources conservation of laboratory animals [J]. Ontogenez, 2015, 46(2): 67-81.
[36] Yang H, Wu Z. Genome editing of pigs for agriculture and biomedicine [J].Front Genet, 2018, 9: 360.
[37] Niu D, Wei HJ, Lin L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 [J]. Science, 2017, 357(6357): 1303-1307.