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阳离子脂质体介导GDNF体内转基因对脊髓损伤后运动神经元的保护作用 被引量：1

Protective effect of cationic liposome-mediated GDNF gene transfer in vivo on motoneurons following spinal cord injury in rats
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摘要 目的 :观察阳离子脂质体介导的胶质细胞源性神经营养因子 (GDNF)体内转基因对大鼠脊髓损伤 (SCI)后伤区脊髓前角运动神经元的影响。方法 :采用改良Nystr m法制备大鼠胸段脊髓后路压迫损伤模型 ,将阳离子脂质体DC Chol和重组质粒 pEGFP GDNFcDNA混合后直接注入大鼠损伤脊髓。利用RT PCR技术和荧光显微镜检测GDNF体内转基因的表达。应用尼氏染色、酶组织化学染色方法观察前角运动神经元死亡的数目和胆碱酯酶(CHE)及酸性磷酸酶 (ACP)的变化。结果 :1周后在注射局部GDNFmRNA和GDNF有较高表达。GDNF体内转基因早期 (1～ 4周 )SCI区前角运动神经元死亡的数目减少 ,CHE和ACP变化的幅度降低。结论 :GDNF体内转基因能减少脊髓不完全性损伤后引起的神经元坏死 ,阳离子脂质体介导GDNF体内转基因治疗创伤性SCI的方法是可行的。 Objective:To observe the effect of cationic liposome mediated GDNF gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats.Method:The SCI model of acute spinal cord posterior compression was established according to the method of Nystrm, then The DC Chol liposomes and recombinant plasmid pEGFP GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA for 1 week after injection was detected by RT PCR and fluorescence microscope. We observed the remaining motoneurons in anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity by using Nissl and enzyme histochemistry staining.Result:RT PCR and Fluorescence observation confirmed the presence of expression of GDNF cDNA for 1 week after injection. It was shown that GDNF cDNA delivery reduced motoneurons death (1～4 week) and the changes of CHE and ACP activity in lesion cord.Conclusion:GDNF gene transfer in vivo may protect motoneurons from death induced by incompleted spinal cord injury. These results suggest that cationic liposome mediated delivery of GDNF cDNA might be a practical method for treating traumatic spinal cord injury.
作者 鲁凯伍 陈哲宇 侯铁胜 傅强 曹莉 金大地
机构地区 第一军医大学南方医院脊柱骨病科 第二军医大学基础医学部神经生物教研室 第二军医大学长海医院骨科
出处 《中国脊柱脊髓杂志》 CAS CSCD 2002年第2期112-115,共4页 Chinese Journal of Spine and Spinal Cord
基金 国家自然科学基金资助项目 (3 0 0 0 0 0 48) 国家重点基础研究"973"基金资助项目 (19990 5 40 0 5 ) 全军"十五"青年基金课题 (0 1Q0 80 )
关键词 胶质细胞源性神经营养因子 脊髓损伤 神经元 阳离子脂质体 基因治疗 Glial cell line derived neurotrophic factor (GDNF) Spinal cord injury Motoneuron Cationic liposome Gene therapy
分类号 R651.205 [医药卫生—外科学]
  • 相关文献

参考文献11

  • 1Baumgartner BJ,Shine HD.Neuroprotection of spinal motoneurons following targeted transduction with an adenoviral vector carrying gene for glial cell line-derived neurotrophic factor[J].Exp Neurol,1998,153:102-112.
  • 2鲁凯伍,陈哲宇,柴延丰,侯铁胜,傅强,路长林,李明.重组大鼠质粒pEGFP-GDNF的构建和在脊髓内表达的实验研究[J].中国神经科学杂志,2001,17(3):226-229. 被引量：6
  • 3陈哲宇,何成,王成海,路长林.人及大鼠胶质细胞源性神经营养因子cDNA的克隆与表达[J].第二军医大学学报,1998,19(1):17-19. 被引量：16
  • 4Nystrom B,Berglund JE,Bergquist E.Methodological analysis of an experimental spinal cord compression model in the rat[J].Acta Neurol Scand,1988,78:460-466.
  • 5Yang K,Clifton GL,Hayes RL.Gene therapy for central nervous injury:The use of cationic liposomes: An invited review[J].J Neurotrauma,1997,14(5):281-297.
  • 6Henderson CE,Philips HS,Pollock RA,et al.GDNF:A potent survival factor for motoneurons present in peripheral nerve and muscle[J].Science,1994,266:1062-1064.
  • 7Baumgartner BJ,Shine HD.Neuroprotection of spinal motoneurons following targeted transduction with an adenoviral vector carrying gene for glial cell line-derived neurotrophic factor[J].Exp Neurol,1998,153:102-112.
  • 8Watabe K,Ohashi T,Sakamoto T,et al.Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor[J].J Neuro Res,2000,60:511-519.
  • 9Yang K,Mu XS,Hayes RL,et al.DC-Chol liposome-mediated gene transfer in rat spinal cord[J].Neuroreport,1997,8(9-10):2355-2358.
  • 10Eigenbrot C,Gerber N.X-ray structure of glial cell-derived neurotrophic 1.9*! resolution and implications for receptor binding[J].Nat Struct Biol,1997,4:435-438.

二级参考文献12

  • 1Yan Q，Nature，1995年，373卷，6512期，341页
  • 2Lin L F，Science，1993年，260卷，5111期，1130页
  • 3Lin LF, Doherty DH, Lile JD, et al. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons [ J ]. Science, 1993,260:1 130-1 132
  • 4Li LX, Wu WT, Lin LF, et al. Rescue of adult mouse motoneurons from injury induced cell death by glial cell line-derived neurotrophic factor[J]. Proc Natl Acad Sci USA, 1995, 92:9 771-9 775.
  • 5Sambrook J, Fritsch EF, Maniaatis T. Molecular Cloning: A Laboratory Manual[M]. 2nd ed, New York: Cold Spring Harbor Laboratory Press, 1989.
  • 6Yang K, Clifton GL, Hayes RL. Gene therapy fooor central nervous injury: The use of cationic liposomes: An invited review[J]. J Neurotrauma, 1997, 14 (5) :281-297.
  • 7Schaar DG, Sieber BA, Sherwood AC, et al. Multiple astrscyte transcripts encode nigral trophic factors in rat and human[ J]. Exp Neurol, 1994, 130: 287-293.
  • 8Prasher DC, Eckenrode VK, Ward WW, et al. Primary structure of the Aequorea victoria green-fluorescent protein[ J]. Gene, 1992, 111(2): 229-231.
  • 9Eigenbrot C, Gerber N. X-ray structure of glial cell-derived neurotrophic 1.9 A resolution and implications for receptor binding[ J ]. Nat Struct Biol, 1997, 4: 435-438.
  • 10Chen ZY , He ZY, He C, et al. Human glial cell line-derived neurotrophic factor: a structure-function analysis[ J ]. Biochem Biophys Res Commun, 2000,268(3): 692-696.

共引文献19

同被引文献25

  • 1Okano H, Ogawa Y, Nakamura M, et al.Transplantation of neural stem cells into the spinal cord after injury[J]. Semin cell Dev Biol,2003,14 (3):191.
  • 2Cartmell T,Southgate T,Rees GS,et al.Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain[J].J Neurosci,1999,19 (4):1517.
  • 3Iwamoto HS,Trapnell BC,McConnell CJ,et al.Pulmonary inflammation associated with repeated, prenatal exposure to an E1,E3-deleted adenoviral vector in sheep[J].Gene Ther,1999,6(1):98.
  • 4Boulis NM,Turner DE,Dice JA,et al.Characterization of adenoviral gene expression in spinal cord after remote vector delivery[J].Neurosurgery,1999,45(1):131.
  • 5O'Leary M, Charlton H.A model for long-term transgene expression in spinal cord regeneration studies[J].Gene Ther,1999,6(8):1351.
  • 6Li Y,Kang J,Friedman J,et al.Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis[J]. Proc Natl Acad Sci USA,1999,96(3):1042.
  • 7Tollefson AE,Hermiston TW,Lichtenstein DL,et al.Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells[J].Nature,1998, 392(6677):726.
  • 8Driesse MJ,Kros JM,Avezaat CJ,et al.Distribution of recombinant adenovirus in the cerebrospinal fluid of nonhuman primates[J].Hum Gene Ther,1999,10(14): 2347.
  • 9Alden TD,Pittman DD,Hankins GR,et al.In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector[J]. Hum Gene Ther,1999,10(13):2245.
  • 10Romero MI, Smith GM.Adenoviral gene transfer into the normal and injured spinal cord:enhanced transgene stability by combined administration of temperature-sensitive virus and transient immune blockade[J].Gene Ther,1998,5(12):1612.

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中国脊柱脊髓杂志
2002年 第2期

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