新生儿缺氧缺血性脑损伤动物模型造模方法述评
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摘要
综述新生儿缺氧缺血性脑损伤(HIBD)动物实验模型的建立方法。制备成功、稳定、可靠的动物模型是进行基础研究的前提条件,目前国内外新生儿HIBD的造模方法主要有:单纯缺氧法、结扎颈总动脉结合缺氧法、宫内感染合并缺氧缺血法、大脑中动脉闭塞法、宫内窘迫法。主要从实验动物的选择、实验方法的设计以及实验评价的标准三个方面来论述各造模方法的优缺点,并针对这些不足提出一些建议和展望。
It summarized the animal model establishing method for neonatal hypoxic- ischemic brain damage( HIBD). A successful,stable and reliable animal model is a prerequisite of basic research. The neonatal HIBD building methods at home and abroad mainly include pure oxygen,carotid artery ligation method combined hypoxia,intrauterine infection with hypoxia- ischemia,middle cerebral artery occlusion and fetal distress method. This article mainly from three aspects discussed the advantages and disadvantages of various building methods,including the choice of experimental animal,the design of the experimental method and experimental evaluation standard,and put forward some suggestions and prospect for these deficiencies.
It summarized the animal model establishing method for neonatal hypoxic- ischemic brain damage( HIBD). A successful,stable and reliable animal model is a prerequisite of basic research. The neonatal HIBD building methods at home and abroad mainly include pure oxygen,carotid artery ligation method combined hypoxia,intrauterine infection with hypoxia- ischemia,middle cerebral artery occlusion and fetal distress method. This article mainly from three aspects discussed the advantages and disadvantages of various building methods,including the choice of experimental animal,the design of the experimental method and experimental evaluation standard,and put forward some suggestions and prospect for these deficiencies.
引文
[1]刘惠,温晓红.脑性瘫痪动物模型鉴定方法研究进展[J].中国实用儿科杂志,2013,28(3):230-233.
[2]Chernick V,Craig RJ.Naloxone reverse neonatal depression caused by fetal asphyxia[J].Science,1982,216:1252-1254.
[3]王志坚,周晓光,刘仁红,等.建立一种改良的新生兔缺氧缺血性脑损伤模型[J].中国实验动物学报,2007,15(4):296-299.
[4]侯新琳,周艳霞,周丛乐,等.新生猪急性缺氧与缺氧缺血模型的比较[J].北京大学学报(医学版),2009,41(6),702-706.
[5]莫国梁.无氧法建立新生鼠缺氧缺血性脑损伤模型的研究[D].重庆:重庆医科大学,2008.
[6]Levine S.Anoxic-ischemic encephalopathy in rats[J].Am J Pathol,1960,36:1-17.
[7]Rice JE 3rd,VannucciRC,Brierley JB,et al.The influence of immaturity on hypoxic-ischemic brain damage in the rat[J].Ann Neuro,1981,9:131-141.
[8]许晓霞,栾佐,古桂雄,等.新生大鼠重度缺氧缺血性脑损伤模型的建立[J].中国新生儿医学杂志,2009,24(3):165-167.
[9]侯伟健,佟浩,柏树令,等.动物低氧实验箱自动控制系统的组建及其在缺氧缺血脑损伤动物模型制作中的应用[J].中国医科大学学报,2013,42(2):138-142.
[10]刘丽旭,杨于嘉,贾延劼,等.新生大鼠缺氧缺血性脑损伤模型的制作[J].湖南医科大学学报,2003,28(2):133-136.
[11]王琍琍,王杨,宣桂华,等.新生大鼠脑缺氧缺血损伤模型的建立[J].安徽医科大学学报,2004,39(4):259-261.
[12]Le Blanc MH,Qian XB,Cai ZW,et al.The effect of glucose during ischemia on brain ATP,lactate,and glutamate in piglets[J].Biol Neonate,1997,72(1):243-254.
[13]周文浩,邵肖梅,李瑾,等.新生猪缺氧缺血脑损伤模型制备的研究[J].中国当代儿科杂志,2003,5(2):113-116.
[14]刘国瑞,李仰康,郭岳霖,等.8%和4%低氧通气状态对新生猪缺氧缺血脑损伤模型制备的影响[J].实用医技杂志,2004,11:2354-2357.
[15]Laptook AR,Stonestreet BS,Willian OH,et al.The effect of carotid artery ligation on brain blood flow in newborn piglets[J].Brain Res,1983,276(1):51-54.
[16]Hisakazu Uehara.Hiroshi Yoshioka.Shoji Kawase.A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion[J].Brain Research,1999,837:213-220.
[17]李湘云,程书卿.缺血缺氧动物实验模型制作分析[J].中国实用神经疾病杂志,2006,9(5):65-66.
[18]陈刚,胡燕荣,钟杰,等.孕鼠腹腔注射脂多糖合并缺氧环境造成宫内胎鼠脑部损伤[J].中国康复理论与实践,2009,15(9):807-809.
[19]Nelson KB,Ellenberg JH.Potentially asphyxiating conditions and spastic cerebral palsy in infants of neonatal birth weight[J].Am J Obstet Gynecol,1998,179:507.
[20]王小阳,朱长连,杨平,等.细菌内毒素增敏缺氧缺血性脑损伤动物模型的建立[J].河南医科大学学报,2001,36(4):401-403.
[21]贺媛媛,栾佐,唐久来,等.两种脑性瘫痪鼠模型的对比[J].中国组织工程研究,2012,16(33):6173-6178.
[22]Renolleau S,Aggoun_Zouaoui D,Ben_Ari Y,et al.A model of transient unilateral focal ischemia with reperfusion in the p7neonatal rat[J].Stroke,1998,29(7):1454-1460.
[23]Sola A,Ragido M,Lee BH,et al.Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activatorof transcription signaling pathway and improvesbrain injury in postnatal day 7 rats[J].PediatrRes,2005,57:481-487.
[24]Tong-Chun Wen,Marta Rogido,Tom Genetta,et al.Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain[J].Neuroscience Letters,2004,355:165-168.
[25]Derugin N,Ferriero DM,Vexler ZS,et al.Neonatal reversible focal cerebral ischemia:a new model[J],Neurosci.Res,1998,32:349-353.
[26]Bjelke,Andersson K,Ogren SO,et al.Asphyctic lesion:proliferation of tyrosine hydroxylase-immunoreactive nerve cell bodies in the rat substantia nigra and functional changes in dopamine neurotransmission[J].Brain Res,1991,543(1):1-9.
[27]薄涛,严超英,霍淑芳,等.结扎孕鼠双侧子宫动脉复制围产期缺氧缺血性脑损伤动物模型[J].中风与神经疾病杂志,2001,18(1):40-43.
[28]巨容,杜江,刘卫鹏,等.阻断子宫血流复制围生期缺氧缺血性脑损伤动物模型[J].广东医学,2006,27(7):953-955.
[29]罗蓉,毛萌,肖侠明,等.钳夹子宫血管致富内生长迟缓幼鼠小脑皮层神经生长因子改变的研究[J].华西医科大学学报,2001,32(1):89-90.
[30]李星儿,袁青,唐纯志,等.延迟5分钟剖宫产造全脑缺氧缺血新生大鼠模型[J].中国实验动物学报,2012,20(4):21-25.
[31]Sidhartha T,Alexander D,Tamas J,et al.Model of cerebral palsy in the perinatal rabbit[J].Child Neurol,2005,20(12):972-979.
[32]Tan S,Zhou F,Nielsen VG,et a1.Sustained hypoxia-ischemia results in reactivenitrogen and oxygen species production and injury in the premature fetal rabbit brain[J].Neuropathol Exp Neurol,1998,57:544-553.
[33]王能里,南燕,柳艳丽,等.近足月胎兔持续宫内缺氧缺血性脑损伤模型的建立[J].中国病理生理杂志,2012,28(4):760-768.
[34]Mallard C,Loeliger M,Copolov D,et a1.Reduced number of neurons in the hippocampus and the cerebellum in the postnatal guinea pig following intrauterine growth restriction[J].Neuroscience,2000,100(2):327.
[35]Gonzalez H,Hunter CJ,Bennet L,et al.Cerebral oxygenation during postasphyxial seizures in near-term fetal sheep[J].Cereb Blood Fiow Metab,2005,25(7):911-918.
[36]Spiegler M,Villapol S,Brain V,et al.Bilateral changes after neonatal ischemia in the P7 rat brain[J].Neuropathol Exp Neurol.2007,66(6):481-490.
[2]Chernick V,Craig RJ.Naloxone reverse neonatal depression caused by fetal asphyxia[J].Science,1982,216:1252-1254.
[3]王志坚,周晓光,刘仁红,等.建立一种改良的新生兔缺氧缺血性脑损伤模型[J].中国实验动物学报,2007,15(4):296-299.
[4]侯新琳,周艳霞,周丛乐,等.新生猪急性缺氧与缺氧缺血模型的比较[J].北京大学学报(医学版),2009,41(6),702-706.
[5]莫国梁.无氧法建立新生鼠缺氧缺血性脑损伤模型的研究[D].重庆:重庆医科大学,2008.
[6]Levine S.Anoxic-ischemic encephalopathy in rats[J].Am J Pathol,1960,36:1-17.
[7]Rice JE 3rd,VannucciRC,Brierley JB,et al.The influence of immaturity on hypoxic-ischemic brain damage in the rat[J].Ann Neuro,1981,9:131-141.
[8]许晓霞,栾佐,古桂雄,等.新生大鼠重度缺氧缺血性脑损伤模型的建立[J].中国新生儿医学杂志,2009,24(3):165-167.
[9]侯伟健,佟浩,柏树令,等.动物低氧实验箱自动控制系统的组建及其在缺氧缺血脑损伤动物模型制作中的应用[J].中国医科大学学报,2013,42(2):138-142.
[10]刘丽旭,杨于嘉,贾延劼,等.新生大鼠缺氧缺血性脑损伤模型的制作[J].湖南医科大学学报,2003,28(2):133-136.
[11]王琍琍,王杨,宣桂华,等.新生大鼠脑缺氧缺血损伤模型的建立[J].安徽医科大学学报,2004,39(4):259-261.
[12]Le Blanc MH,Qian XB,Cai ZW,et al.The effect of glucose during ischemia on brain ATP,lactate,and glutamate in piglets[J].Biol Neonate,1997,72(1):243-254.
[13]周文浩,邵肖梅,李瑾,等.新生猪缺氧缺血脑损伤模型制备的研究[J].中国当代儿科杂志,2003,5(2):113-116.
[14]刘国瑞,李仰康,郭岳霖,等.8%和4%低氧通气状态对新生猪缺氧缺血脑损伤模型制备的影响[J].实用医技杂志,2004,11:2354-2357.
[15]Laptook AR,Stonestreet BS,Willian OH,et al.The effect of carotid artery ligation on brain blood flow in newborn piglets[J].Brain Res,1983,276(1):51-54.
[16]Hisakazu Uehara.Hiroshi Yoshioka.Shoji Kawase.A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion[J].Brain Research,1999,837:213-220.
[17]李湘云,程书卿.缺血缺氧动物实验模型制作分析[J].中国实用神经疾病杂志,2006,9(5):65-66.
[18]陈刚,胡燕荣,钟杰,等.孕鼠腹腔注射脂多糖合并缺氧环境造成宫内胎鼠脑部损伤[J].中国康复理论与实践,2009,15(9):807-809.
[19]Nelson KB,Ellenberg JH.Potentially asphyxiating conditions and spastic cerebral palsy in infants of neonatal birth weight[J].Am J Obstet Gynecol,1998,179:507.
[20]王小阳,朱长连,杨平,等.细菌内毒素增敏缺氧缺血性脑损伤动物模型的建立[J].河南医科大学学报,2001,36(4):401-403.
[21]贺媛媛,栾佐,唐久来,等.两种脑性瘫痪鼠模型的对比[J].中国组织工程研究,2012,16(33):6173-6178.
[22]Renolleau S,Aggoun_Zouaoui D,Ben_Ari Y,et al.A model of transient unilateral focal ischemia with reperfusion in the p7neonatal rat[J].Stroke,1998,29(7):1454-1460.
[23]Sola A,Ragido M,Lee BH,et al.Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activatorof transcription signaling pathway and improvesbrain injury in postnatal day 7 rats[J].PediatrRes,2005,57:481-487.
[24]Tong-Chun Wen,Marta Rogido,Tom Genetta,et al.Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain[J].Neuroscience Letters,2004,355:165-168.
[25]Derugin N,Ferriero DM,Vexler ZS,et al.Neonatal reversible focal cerebral ischemia:a new model[J],Neurosci.Res,1998,32:349-353.
[26]Bjelke,Andersson K,Ogren SO,et al.Asphyctic lesion:proliferation of tyrosine hydroxylase-immunoreactive nerve cell bodies in the rat substantia nigra and functional changes in dopamine neurotransmission[J].Brain Res,1991,543(1):1-9.
[27]薄涛,严超英,霍淑芳,等.结扎孕鼠双侧子宫动脉复制围产期缺氧缺血性脑损伤动物模型[J].中风与神经疾病杂志,2001,18(1):40-43.
[28]巨容,杜江,刘卫鹏,等.阻断子宫血流复制围生期缺氧缺血性脑损伤动物模型[J].广东医学,2006,27(7):953-955.
[29]罗蓉,毛萌,肖侠明,等.钳夹子宫血管致富内生长迟缓幼鼠小脑皮层神经生长因子改变的研究[J].华西医科大学学报,2001,32(1):89-90.
[30]李星儿,袁青,唐纯志,等.延迟5分钟剖宫产造全脑缺氧缺血新生大鼠模型[J].中国实验动物学报,2012,20(4):21-25.
[31]Sidhartha T,Alexander D,Tamas J,et al.Model of cerebral palsy in the perinatal rabbit[J].Child Neurol,2005,20(12):972-979.
[32]Tan S,Zhou F,Nielsen VG,et a1.Sustained hypoxia-ischemia results in reactivenitrogen and oxygen species production and injury in the premature fetal rabbit brain[J].Neuropathol Exp Neurol,1998,57:544-553.
[33]王能里,南燕,柳艳丽,等.近足月胎兔持续宫内缺氧缺血性脑损伤模型的建立[J].中国病理生理杂志,2012,28(4):760-768.
[34]Mallard C,Loeliger M,Copolov D,et a1.Reduced number of neurons in the hippocampus and the cerebellum in the postnatal guinea pig following intrauterine growth restriction[J].Neuroscience,2000,100(2):327.
[35]Gonzalez H,Hunter CJ,Bennet L,et al.Cerebral oxygenation during postasphyxial seizures in near-term fetal sheep[J].Cereb Blood Fiow Metab,2005,25(7):911-918.
[36]Spiegler M,Villapol S,Brain V,et al.Bilateral changes after neonatal ischemia in the P7 rat brain[J].Neuropathol Exp Neurol.2007,66(6):481-490.