DhHP-6对宫内窘迫胎鼠脑保护作用的研究
摘要
目的:研究亚血红素六肽(DhHP-6)对宫内缺氧缺血胎鼠脑组织自由基和细胞凋亡的影响,探讨DhHP-6对宫内窘迫胎鼠脑组织的保护作用。
方法:Wistay雌性大白鼠,于妊娠第19d通过无损伤动脉钳钳夹双侧子宫、卵巢血管建立缺血缺氧宫内窘迫模型,将母鼠随机分为A组(假手术组),B组(模型组),DhHP-6治疗组:又分为HI前30min和HI后立即给药组(即C、D组)。此后实验用母鼠均关腹放回原饲养环境中24h后,立即剖宫取胎,每组随即抽取10只胎鼠断头取脑组织制备标本,取胎脑冠状面切片,行HE染色和TUNEL染色法检查,高倍镜下观察胎鼠脑组织常规病理改变与海马区神经细胞凋亡情况,剩余胎鼠脑组织经冻存后,制作匀浆后以比色法测定MDA含量。
结果:胎鼠死亡率、MDA含量、海马区细胞凋亡数B组与A组比较,差异具有显著性(D＜0.01);C组、D组与B组比较,存在差异性(p＜0.01、p＜0.05);D组MDA含量、细胞凋亡数与C组比较差异具有显著性(p＜0.01)。
结论:DhHP-6有抗氧化和较强的氧自由基清除作用,同时减轻脑组织在宫内已加重的细胞凋亡损伤;缺氧缺血性脑损伤前用药比其后用药效果更佳。
Object: To investigate the effects of DhHP-6 on free radical and apoptosis of fetal rat brain sufered from intrauterine hypoxic-ischemic injury,so as to explore the neuroprotective mechanisms of DhHP-6.
Methods: Wistay female rats, In the 19d of pregnancy, through non-invasive clamp-clamp bilateral uterine artery arterio-venous, ovarian artery and vein to establish model of hypoxic-ischemic fetal distress,the rats were randomly divided into A group (control group), B group (model group), DhHP-6 group treatment group:divided into 30min before hypoxia-ischemia and immediately after HI treatment group (that is, C, D group). Experimental rats were then abdominal closure feeding back into the original environment after 24h,n each group randomly selected 10 fetal rat, take immediate caesarean births, broken prepared from brain tissue specimens,the pathological changes of brain tissues were observed upder light microscope by HE staining and TUNEL assay ,the remaining fetal rat brain tissue after cryopreservation, the production was detected after homogenate MDA content.
Results: Fetal rat mortality, MDA content in hippocampus of apoptosis in several B group and A group, the difference was significant (p <0.01);C group, D group and B group, the existence of differences (p <0.01, p <0.05);MDA content in group D, the number of apoptosis compared with the C group difference was significant (p <0.01).
Conclusion: DhHP-6 protects fetal brain against oxidative damage and lowers the number of apoptosis cells of fetal brain;Hypoxic-ischemic brain damage before the effects of drug use better than later.
方法:Wistay雌性大白鼠,于妊娠第19d通过无损伤动脉钳钳夹双侧子宫、卵巢血管建立缺血缺氧宫内窘迫模型,将母鼠随机分为A组(假手术组),B组(模型组),DhHP-6治疗组:又分为HI前30min和HI后立即给药组(即C、D组)。此后实验用母鼠均关腹放回原饲养环境中24h后,立即剖宫取胎,每组随即抽取10只胎鼠断头取脑组织制备标本,取胎脑冠状面切片,行HE染色和TUNEL染色法检查,高倍镜下观察胎鼠脑组织常规病理改变与海马区神经细胞凋亡情况,剩余胎鼠脑组织经冻存后,制作匀浆后以比色法测定MDA含量。
结果:胎鼠死亡率、MDA含量、海马区细胞凋亡数B组与A组比较,差异具有显著性(D＜0.01);C组、D组与B组比较,存在差异性(p＜0.01、p＜0.05);D组MDA含量、细胞凋亡数与C组比较差异具有显著性(p＜0.01)。
结论:DhHP-6有抗氧化和较强的氧自由基清除作用,同时减轻脑组织在宫内已加重的细胞凋亡损伤;缺氧缺血性脑损伤前用药比其后用药效果更佳。
Object: To investigate the effects of DhHP-6 on free radical and apoptosis of fetal rat brain sufered from intrauterine hypoxic-ischemic injury,so as to explore the neuroprotective mechanisms of DhHP-6.
Methods: Wistay female rats, In the 19d of pregnancy, through non-invasive clamp-clamp bilateral uterine artery arterio-venous, ovarian artery and vein to establish model of hypoxic-ischemic fetal distress,the rats were randomly divided into A group (control group), B group (model group), DhHP-6 group treatment group:divided into 30min before hypoxia-ischemia and immediately after HI treatment group (that is, C, D group). Experimental rats were then abdominal closure feeding back into the original environment after 24h,n each group randomly selected 10 fetal rat, take immediate caesarean births, broken prepared from brain tissue specimens,the pathological changes of brain tissues were observed upder light microscope by HE staining and TUNEL assay ,the remaining fetal rat brain tissue after cryopreservation, the production was detected after homogenate MDA content.
Results: Fetal rat mortality, MDA content in hippocampus of apoptosis in several B group and A group, the difference was significant (p <0.01);C group, D group and B group, the existence of differences (p <0.01, p <0.05);MDA content in group D, the number of apoptosis compared with the C group difference was significant (p <0.01).
Conclusion: DhHP-6 protects fetal brain against oxidative damage and lowers the number of apoptosis cells of fetal brain;Hypoxic-ischemic brain damage before the effects of drug use better than later.
引文
[1]Baqenholm R,vilssomcuA,Kiellmer l.Fonnation of free radicals in hypoxic ische-ischemic ischemic brain damaqe in the meonatal rat[J].Brain.Res,1997,773:132-138.
[2]Meada M.Anatysis of oxidative in rat fetus induced bu clamping and reperfu-sion of uterine vessels.Nippon sanka Fajinka Gakkai zassni,1996,48:111-117.
[3]Baqenholm R,Nilssom UA,Gotborq CW,etal.Free radicals are formed in tne brain of fetal sheep durinq reperfu-sion after cerebrad ischemia.pediatr Res,1998,43:271-275。
[4]Liu PK,Grossman RG,Hsu CY,et al.Ischemic injury and faulty gene transcripts in the brain Trends Neurisei,2001,24(10):581-588.
[5]秦丽娜,冯爱华,杨传华,等.宫内窘迫新生儿脐动脉血超氧化物歧化酶及丙二醛检测的临床意义,中华妇产科杂志,2005,40(5):312-314.
[6]宋微微,高红,韩玉坤,等.胎鼠宫内缺氧缺血后脑细胞凋亡及相关基因的表达.中华妇产科杂志,2000,35(5):294-295.
[7]Nano and Asada,Vidal P,Heitz A,Biochemistry,1981,36(37):1179-1187
[8]H.Weller,Adv,Mater.1993,5,88
[9]I.Mekis,D.V.Talapin,A.Kornowski,M.Haase,H.Weller,JA.ki,KornM.Ha,owsase,H.Weller,J.Phys.Chem.B,2003,107,7454
[10]J.Rodriguez-Viejo,K.F.Jensen,H.Mattoussi,J.Michel,B.O.Dabbousi,M.G.Bawendi,Appl.Phys.Lett.1997,70,2132
[11]闫玉梅.过氧化物模拟酶对H_2O_2诱导的心肌细胞氧化损伤保护作用的研究[D].中国优秀博硕士学位论文全文数据库(硕士),2006(10).
[12]张研.APX模拟酶(DhHP-6)对肝移植供体保护作用方面的研究(D),中国优秀博硕士学位论文全文数据库(博士),2007(6).
[13]俞丹,毛萌,周晖,等.宫内缺血缺氧致胚鼠脑细胞损伤凋亡的实验研究[J]. 四川大学学报(医学版),2004,35(3):354-357.
[14]Rice JE,VannucciRC,and Brierley JB.The influence of immaturity on hypoxic ischemic brain damage in the rat.Ann Neurol,1981,9:131-141.
[15]De Haan HH,Gunn AJ,Williams CE,et al.Briedf repeated unbilical cord occlusions cause sustained cytotoxic cerebral edema and focal infarcts in near term fetal lambs.Pediatr Res,1997,41:96-104.
[16]Mallard C,Loeliger M,Copolov D,et al.Reduced number of neurons in the Hippocampus and the cerebellum in the postnatal guinea pig Follwoing intrauterine growth restriction.Neurosciece,2000,100(2):327-333.
[17]Trescher WH,Lehman RA,Vannucci RC,The influence of growth retardation on Perinatal hypocic-ischemic brain damage.Early Hum Dev,1990,21:165-173.
[18]杜鹃,尚涛,魏轶兵,等.子宫胎盘缺血对胎鼠体重及神经系统发育影响的研究,中华妇产科杂志,2004,35(3):354-357.
[19]薄涛,严超英,李巍,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,2001,18(1):40-41.
[20]Vannucci RC,Perlman JM.Interventions for perinatal hupoxic ischemic encephal -opathy.Pediatrics,1997,100(6):1004-1014.
[21]张鸿.银杏叶提取物对大鼠脑缺血再灌注后自由基损伤的保护作用.中国康复,2004,19(2):73-74.
[22]Dhalla NS,Elmoselhi AB,Hata T,Makimo N,Card Res,2000,47(3):446-56.
[23]关树文,王立成,杨明等.DhHp滴眼液对实验性半乳糖白内障的防治作用.中国老年学杂志,2009,29(3):286-288.
[24]Kitagawa K,Matsumoto M.Tsujimoto Y.et al.Ameloration of hipocampal neuronal damage after global ischemia by neuronal overexpression of Bcl-2 in transgenic mice,Stroke.1998;29(12):2616.
[25]Endres M.Namura S.Shimizu-Sasamata M.etal.attenuation of delayed death after mild focal ischemia in mice by inhibition of the caspase family.J Cereb Flow Metab,1998,118(3):238.
[26]王菊莉,韩玉坤.新生大鼠缺氧缺血性脑损伤神经细胞凋亡时程.新生儿科杂志,2003,18(3):111-113.
[27]Charriaut-Marlangue C,Margail I,Represa A,et al.Apoptosis andnecrosis after Reversible focal ischemis:an in situ DNA fragmentation analysis.J Cereb blood Flow Metab.1996,16(2):186-194.
[28]黄广,陈映曼,肖育.新生大鼠缺氧缺血性脑损伤后细胞凋亡与自由基损伤机制研究.2008,14(3):225-258.
[1]Temesvari P,Karg E,Bodi L,et al.Impaired early neurologic outcome in newborn piglets reoxygenated with100%oxygen compared with room air after pneumothorax-induceda sphyxia.Pe diatr Res,2001;49(6):81 29.
[2]Vannucci RC.Hypoxic-ischemic encephalopathy.Am J Perina-tol,2000,17:113-120.
[3]鲁利群,范建义,郑燕,等.围生期缺氧缺氧性脑损伤的研究进展[J].西南国防医药,2007,17(4):506-508.
[4]Gunn AJ,Gunn TR,Gunning MI,et al.Neuroprotection with prolonged head cooling stared before postischemic seizures in fetal sheep.Pediatrics,1998,102:1098-1106.
[5]胡志云,姜长斌,尹琳,等.氟利桂嗪对脑海马迟发性神经元死亡沙土鼠空间分辨学习能力的影响[J].中国临床康复,2005,9(20):145-147.
[6]胡伟,赵聪敏,巩守平.神经生长因子和神经节苷脂对新生鼠缺氧缺血醒脑损伤海马神经元的保护作用[J].第三军医大学学报,2006,28(24):2430-2433.
[7]Hamada Y,Hayakawa T,Hattori H,et al.Inhihitor of nitric oxide synthesis reduces hypoxic-ischemic brain injury in the neonatal rat.Pediatr Res,1994,35:10-14.
[8]Thordstein M,Baqenholm R,Thirinqerk,etal.Scarenqwesof free oxyqen radicals in combination with maqnesiam wmeliorate perinatal hypoxic -ischemic brain damaqe in the rat.pediatr Res,1993,34:23-26。
[9]陈继昌.亚低温治疗缺氧缺血醒脑损伤研究进展[J].医学综述,2001,7(8):487。
[10]岳筱莉,宋文爱.1,6二磷酸果糖治疗新生儿缺氧缺血性脑病疗效观察[J].临床医药实践杂志,2008,7(17):538-539.
[11]Dorrepaal CA,Steendijk P,Baan J,et al.Inhibition of nitric synthesis following severe hypoxia-ischemia restores autoregula-tion of cerebral blood fiow in newborn lambs[J].Early Hum Dev,2001,60(3):159-170.
[12]Yufu K,hoh T,Edamatsu R,et al.FaCfect of hyperbaric oxygenation on the Na(+),K+(-)ⅣlHlse and metnbrane fluidity of cerebro-cortieal membra/le8after Experimental subarachnoid hemorrhage[J].Neurochem Res,1993,18(9):1033-1039.
[13]Badr AE,Yin W,Mychaskiw G,et al.Effect of hyperlmric oxygen on striatal metabolites:a microdialysis study in awake freely moving rats after MCA occlusion[J].Brain Res,2001,916(1-2):85-90.
[14]Konda A,Baba S,1waki T,et al.Hyperbaric oxygenation prevents delayed neuronal death following transientischemia in the gerbil hippocampus[J].Neuropathol Appl Neumbiol,1996,22(4):350-360.
[15]Atochin DN,Fisher D,Thorn SR,et a l.Hyperbaric oxygen Inhibits neutrophil infiltration and reduces postisebemic brain injury in rats[J].Ross Fiziol Zhim Sechenova,2001,87(8):1118-1125.
[16]刘美娜.高压氧防治缺氧缺血醒脑损伤的研究进展[J].国外医学儿科学分册,2004,31(3):123-125.
[17]李力仙,赵世光,叶远柱等.亚低温在脑缺血再灌注损伤中的作用[J].中国微侵袭神经外科(CMINS),2004,9(4):184-186.
[18]Craig CG,Tropa pe V,Morshead CM,et al.In vivo growth factors expression ofen dogenous subependymal neura precursor cellpopuhtioas in the adult mouse brain.J Neurosci,1996,16:2649-2658.
[19]Enghnd U Fricker GayesRA,Lundberg C,et al.Transplanta tion of hu- man neural progenitor cells into the neonatal rat brain extensive migration and differentiation with long-distance axonal projections.Exp Neurol,2002.173:1-21.
[20]Fu H Oiu M.Migration and diferen tiation of Nkx-2.2~+ oligoden-drocyte progenitors in embryonic chicken retina Brain Res Dev Brain Res.2001.129:115-118.
[21]Fukunaga A,Uchida K,Hara K,et al.Diferentiation and angiogenesisof central nervous system stern cells implanted with mesenchy nei-nto ischemic rat brain. CELL Transplant.1999.8:435-441.
[22]Park KI,Jensen FE,Stieg PE,et al.Tran splantation of neurotro-phin-3(NT-3) expressing neural stem-like cells into hypoxicischemic brain iniury.Soc Neurosci Abstr.1997.23:346-349.
[23]Andsberg G,Kokaia Z,Bjorkhnd A,et al.Amelioration of ischemic induced neuronal death in the rat striatum by NGF-secreting neural stern cells.Eur J Neurosci,1998.10:2026 -2036.
[24]Castilo-Melendez M,Yan E,Walker DW.Expression of erythropoietin and its receptor in the brain of late-gestation fetal sheep,and responses to asphyxia caused by umbilical cord occlusion.Dev Neurosci,2005,27(2-4):220-7.
[25]Marti HH,Bemaudin M,Petrt E,et al.Neuroprotection and angioglnesis dual role of erythropoietin in brain ischemia[J].Physiol sci,2000,15:225 -229.
[26]Kwon DN,Song H,Park JY,et al.dynamic control of oligosaccharide modification in the Mammary Gland:linking Recombinant Human erythropoietin Functional analysis of transgenic Mouse Milk-Derived bEPO.Transgenic Res,2006,15(1):37-55.
[27]邱莉,黄俊山.新生儿缺氧缺血性脑病治疗研究进展[J].中外健康文摘,2008,5(8):11-12.
[28]谭玲,陈娟,廖志.促红细胞生成素对新生大鼠缺氧缺血醒脑损伤海马区神经细胞掉的影响[J].四川医学,2006,27(10):1000-1001.
[29]陈敏榕.早期干预对缺氧缺血性脑损伤大鼠脑功能及神经功能的影响[D].万方硕博士论文.2004(6).
[30]Nakamura M,Raghupathi R,Merry DE,etal.Overe of antioxidant enzyme action of Bcl-2 is neuroprotective after experimental brain injury intransgenicm ice[J].Compneurol,2000,41(4):681-692.
[2]Meada M.Anatysis of oxidative in rat fetus induced bu clamping and reperfu-sion of uterine vessels.Nippon sanka Fajinka Gakkai zassni,1996,48:111-117.
[3]Baqenholm R,Nilssom UA,Gotborq CW,etal.Free radicals are formed in tne brain of fetal sheep durinq reperfu-sion after cerebrad ischemia.pediatr Res,1998,43:271-275。
[4]Liu PK,Grossman RG,Hsu CY,et al.Ischemic injury and faulty gene transcripts in the brain Trends Neurisei,2001,24(10):581-588.
[5]秦丽娜,冯爱华,杨传华,等.宫内窘迫新生儿脐动脉血超氧化物歧化酶及丙二醛检测的临床意义,中华妇产科杂志,2005,40(5):312-314.
[6]宋微微,高红,韩玉坤,等.胎鼠宫内缺氧缺血后脑细胞凋亡及相关基因的表达.中华妇产科杂志,2000,35(5):294-295.
[7]Nano and Asada,Vidal P,Heitz A,Biochemistry,1981,36(37):1179-1187
[8]H.Weller,Adv,Mater.1993,5,88
[9]I.Mekis,D.V.Talapin,A.Kornowski,M.Haase,H.Weller,JA.ki,KornM.Ha,owsase,H.Weller,J.Phys.Chem.B,2003,107,7454
[10]J.Rodriguez-Viejo,K.F.Jensen,H.Mattoussi,J.Michel,B.O.Dabbousi,M.G.Bawendi,Appl.Phys.Lett.1997,70,2132
[11]闫玉梅.过氧化物模拟酶对H_2O_2诱导的心肌细胞氧化损伤保护作用的研究[D].中国优秀博硕士学位论文全文数据库(硕士),2006(10).
[12]张研.APX模拟酶(DhHP-6)对肝移植供体保护作用方面的研究(D),中国优秀博硕士学位论文全文数据库(博士),2007(6).
[13]俞丹,毛萌,周晖,等.宫内缺血缺氧致胚鼠脑细胞损伤凋亡的实验研究[J]. 四川大学学报(医学版),2004,35(3):354-357.
[14]Rice JE,VannucciRC,and Brierley JB.The influence of immaturity on hypoxic ischemic brain damage in the rat.Ann Neurol,1981,9:131-141.
[15]De Haan HH,Gunn AJ,Williams CE,et al.Briedf repeated unbilical cord occlusions cause sustained cytotoxic cerebral edema and focal infarcts in near term fetal lambs.Pediatr Res,1997,41:96-104.
[16]Mallard C,Loeliger M,Copolov D,et al.Reduced number of neurons in the Hippocampus and the cerebellum in the postnatal guinea pig Follwoing intrauterine growth restriction.Neurosciece,2000,100(2):327-333.
[17]Trescher WH,Lehman RA,Vannucci RC,The influence of growth retardation on Perinatal hypocic-ischemic brain damage.Early Hum Dev,1990,21:165-173.
[18]杜鹃,尚涛,魏轶兵,等.子宫胎盘缺血对胎鼠体重及神经系统发育影响的研究,中华妇产科杂志,2004,35(3):354-357.
[19]薄涛,严超英,李巍,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,2001,18(1):40-41.
[20]Vannucci RC,Perlman JM.Interventions for perinatal hupoxic ischemic encephal -opathy.Pediatrics,1997,100(6):1004-1014.
[21]张鸿.银杏叶提取物对大鼠脑缺血再灌注后自由基损伤的保护作用.中国康复,2004,19(2):73-74.
[22]Dhalla NS,Elmoselhi AB,Hata T,Makimo N,Card Res,2000,47(3):446-56.
[23]关树文,王立成,杨明等.DhHp滴眼液对实验性半乳糖白内障的防治作用.中国老年学杂志,2009,29(3):286-288.
[24]Kitagawa K,Matsumoto M.Tsujimoto Y.et al.Ameloration of hipocampal neuronal damage after global ischemia by neuronal overexpression of Bcl-2 in transgenic mice,Stroke.1998;29(12):2616.
[25]Endres M.Namura S.Shimizu-Sasamata M.etal.attenuation of delayed death after mild focal ischemia in mice by inhibition of the caspase family.J Cereb Flow Metab,1998,118(3):238.
[26]王菊莉,韩玉坤.新生大鼠缺氧缺血性脑损伤神经细胞凋亡时程.新生儿科杂志,2003,18(3):111-113.
[27]Charriaut-Marlangue C,Margail I,Represa A,et al.Apoptosis andnecrosis after Reversible focal ischemis:an in situ DNA fragmentation analysis.J Cereb blood Flow Metab.1996,16(2):186-194.
[28]黄广,陈映曼,肖育.新生大鼠缺氧缺血性脑损伤后细胞凋亡与自由基损伤机制研究.2008,14(3):225-258.
[1]Temesvari P,Karg E,Bodi L,et al.Impaired early neurologic outcome in newborn piglets reoxygenated with100%oxygen compared with room air after pneumothorax-induceda sphyxia.Pe diatr Res,2001;49(6):81 29.
[2]Vannucci RC.Hypoxic-ischemic encephalopathy.Am J Perina-tol,2000,17:113-120.
[3]鲁利群,范建义,郑燕,等.围生期缺氧缺氧性脑损伤的研究进展[J].西南国防医药,2007,17(4):506-508.
[4]Gunn AJ,Gunn TR,Gunning MI,et al.Neuroprotection with prolonged head cooling stared before postischemic seizures in fetal sheep.Pediatrics,1998,102:1098-1106.
[5]胡志云,姜长斌,尹琳,等.氟利桂嗪对脑海马迟发性神经元死亡沙土鼠空间分辨学习能力的影响[J].中国临床康复,2005,9(20):145-147.
[6]胡伟,赵聪敏,巩守平.神经生长因子和神经节苷脂对新生鼠缺氧缺血醒脑损伤海马神经元的保护作用[J].第三军医大学学报,2006,28(24):2430-2433.
[7]Hamada Y,Hayakawa T,Hattori H,et al.Inhihitor of nitric oxide synthesis reduces hypoxic-ischemic brain injury in the neonatal rat.Pediatr Res,1994,35:10-14.
[8]Thordstein M,Baqenholm R,Thirinqerk,etal.Scarenqwesof free oxyqen radicals in combination with maqnesiam wmeliorate perinatal hypoxic -ischemic brain damaqe in the rat.pediatr Res,1993,34:23-26。
[9]陈继昌.亚低温治疗缺氧缺血醒脑损伤研究进展[J].医学综述,2001,7(8):487。
[10]岳筱莉,宋文爱.1,6二磷酸果糖治疗新生儿缺氧缺血性脑病疗效观察[J].临床医药实践杂志,2008,7(17):538-539.
[11]Dorrepaal CA,Steendijk P,Baan J,et al.Inhibition of nitric synthesis following severe hypoxia-ischemia restores autoregula-tion of cerebral blood fiow in newborn lambs[J].Early Hum Dev,2001,60(3):159-170.
[12]Yufu K,hoh T,Edamatsu R,et al.FaCfect of hyperbaric oxygenation on the Na(+),K+(-)ⅣlHlse and metnbrane fluidity of cerebro-cortieal membra/le8after Experimental subarachnoid hemorrhage[J].Neurochem Res,1993,18(9):1033-1039.
[13]Badr AE,Yin W,Mychaskiw G,et al.Effect of hyperlmric oxygen on striatal metabolites:a microdialysis study in awake freely moving rats after MCA occlusion[J].Brain Res,2001,916(1-2):85-90.
[14]Konda A,Baba S,1waki T,et al.Hyperbaric oxygenation prevents delayed neuronal death following transientischemia in the gerbil hippocampus[J].Neuropathol Appl Neumbiol,1996,22(4):350-360.
[15]Atochin DN,Fisher D,Thorn SR,et a l.Hyperbaric oxygen Inhibits neutrophil infiltration and reduces postisebemic brain injury in rats[J].Ross Fiziol Zhim Sechenova,2001,87(8):1118-1125.
[16]刘美娜.高压氧防治缺氧缺血醒脑损伤的研究进展[J].国外医学儿科学分册,2004,31(3):123-125.
[17]李力仙,赵世光,叶远柱等.亚低温在脑缺血再灌注损伤中的作用[J].中国微侵袭神经外科(CMINS),2004,9(4):184-186.
[18]Craig CG,Tropa pe V,Morshead CM,et al.In vivo growth factors expression ofen dogenous subependymal neura precursor cellpopuhtioas in the adult mouse brain.J Neurosci,1996,16:2649-2658.
[19]Enghnd U Fricker GayesRA,Lundberg C,et al.Transplanta tion of hu- man neural progenitor cells into the neonatal rat brain extensive migration and differentiation with long-distance axonal projections.Exp Neurol,2002.173:1-21.
[20]Fu H Oiu M.Migration and diferen tiation of Nkx-2.2~+ oligoden-drocyte progenitors in embryonic chicken retina Brain Res Dev Brain Res.2001.129:115-118.
[21]Fukunaga A,Uchida K,Hara K,et al.Diferentiation and angiogenesisof central nervous system stern cells implanted with mesenchy nei-nto ischemic rat brain. CELL Transplant.1999.8:435-441.
[22]Park KI,Jensen FE,Stieg PE,et al.Tran splantation of neurotro-phin-3(NT-3) expressing neural stem-like cells into hypoxicischemic brain iniury.Soc Neurosci Abstr.1997.23:346-349.
[23]Andsberg G,Kokaia Z,Bjorkhnd A,et al.Amelioration of ischemic induced neuronal death in the rat striatum by NGF-secreting neural stern cells.Eur J Neurosci,1998.10:2026 -2036.
[24]Castilo-Melendez M,Yan E,Walker DW.Expression of erythropoietin and its receptor in the brain of late-gestation fetal sheep,and responses to asphyxia caused by umbilical cord occlusion.Dev Neurosci,2005,27(2-4):220-7.
[25]Marti HH,Bemaudin M,Petrt E,et al.Neuroprotection and angioglnesis dual role of erythropoietin in brain ischemia[J].Physiol sci,2000,15:225 -229.
[26]Kwon DN,Song H,Park JY,et al.dynamic control of oligosaccharide modification in the Mammary Gland:linking Recombinant Human erythropoietin Functional analysis of transgenic Mouse Milk-Derived bEPO.Transgenic Res,2006,15(1):37-55.
[27]邱莉,黄俊山.新生儿缺氧缺血性脑病治疗研究进展[J].中外健康文摘,2008,5(8):11-12.
[28]谭玲,陈娟,廖志.促红细胞生成素对新生大鼠缺氧缺血醒脑损伤海马区神经细胞掉的影响[J].四川医学,2006,27(10):1000-1001.
[29]陈敏榕.早期干预对缺氧缺血性脑损伤大鼠脑功能及神经功能的影响[D].万方硕博士论文.2004(6).
[30]Nakamura M,Raghupathi R,Merry DE,etal.Overe of antioxidant enzyme action of Bcl-2 is neuroprotective after experimental brain injury intransgenicm ice[J].Compneurol,2000,41(4):681-692.