期刊文献+

转化生长因子-β1对脊髓损伤后神经细胞凋亡的影响 被引量:2

The effects of TGF-β1 on the apoptosis of nerve cells after spinal cord injury in rats
原文传递
导出
摘要 目的探讨转化生长因子(Transforming growth factor-β1,TGF-β1)对大鼠脊髓损伤后神经细胞凋亡及神经动能恢复的影响。方法采用改良Allen’s撞击法制作脊髓损伤大鼠模型,根据干预方式不同随机分为对照组、模型组、TGF—β1治疗组(渗透微泵持续蛛网膜下腔泵入1μg/hTGF—β1)、TGF-β1抗体组(渗透微泵持续蛛网膜下腔泵入1μg/h TGF—β1中和抗体),按设定的不同时间点随机处死各组的实验动物,取材。应用TUNEL法、RT—PCR、Western blot和免疫组织化学染色分别检测不同组别在神经细胞凋亡,脊髓组织细胞中TGF—β1和Fas的mRNA及蛋白质表达差异。通过BBB运动功能评分法评估大鼠后肢运动功能恢复情况。结果脊髓损伤后TGF—β1和Fas表达时间依赖性增加,Fas表达24h达高峰,TGF—β1表达7d达高峰。脊髓损伤后神经细胞凋亡增加,其中8h神经元凋亡明显,7d神经胶质细胞凋亡明显。局部应用TGF-β1,可显著下调损伤脊髓组织Fas表达,减少8h和7d时神经元凋亡及神经胶质细胞凋亡数量,BBB运动功能评分结果显示,TGF—β1治疗组大鼠后肢运动功能明显改善(P〈0.01)。结论脊髓损伤部位应用TGF-β1可抑制FasmRNA及蛋白质的表达,减少脊髓损伤部位神经细胞的凋亡,有利于促进脊髓神经功能的恢复。 Objective To investigate the effects of exogenous transforming growth factor β1 on the apoptosis of nerve cells and its functions following spinal cord injury in rats. Methods Ninety-six male Wistar rats were randomly divided into 4 groups: group A (control group), group B (spinal cord injured group), group C (spinal cord injuried +TGF-β1 treated group), group D (spinal cord injuried +anti-TGF-β1 treated group). The rat model of spinal cord injury was found by the Allen's method. In group C and D, drugs were injected into subarachnoid cavity continuously by minipump. The changes of spinal cord were observed by HE staining. Nerve cells apoptosis was detected by transferase-medi-ated dUTP nick end labeling (TNUEL) method and the expression of cell apoptosis factor Fas by immunohistochemistry staining. Functional recovery of hind limbs was measured by Basso-Beattie-Bresnahan locomotor open field behavioral rating test. Results The expression of TGF-β1 and Fas increased following spinal cord injury. The amount of TGF-β1 and Fas reached the peak 7days and lday after injury. The apoptosis of neuron had increased and peaked 8 hours after injury. The apoptosis of neuroglia cells had increased and peaked 7 dayss after injury. The slight changes was found in spinal cord in group C. Both of the number of apoptosis of nerve cells and expression of the apoptosis factor (Fas) decreased significantly; compare with group B and D. The BBB score was higher in group C than that in group B and D. Conclusion TGF-β1 can improve the functional recovery of spinal cord by inhibiting the nerve cell apoptosis after the spinal cord injury.
出处 《中华骨科杂志》 CAS CSCD 北大核心 2011年第12期1344-1351,共8页 Chinese Journal of Orthopaedics
关键词 脊髓损伤 转化生长因子-Β1 细胞凋亡 Spinal cord injuries Transforming growth factor-batal Apoptosis
  • 相关文献

参考文献2

二级参考文献21

  • 1Jeffrey L, Goldberg, Ben A. The relationship between neuronal survival and regenaration[J]. Annu Rev Neurosci, 2000,23(2):579-612.
  • 2Mclennan IS, Koishi K. The transforming growth factor-betas: multifaceted regulations of the development and maintenance of skeletal muscles,motoneurons and Schwann cells[J]. Int J Dev Biol, 2002,46(4):559-567.
  • 3Zhu Y, Culmsee C, Klumpp S, et al. Neuroprotection by transforming growth factor beta 1 involves activation of nuclear factor-kappa B through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein linase-extracellular-signal regulated kinase1,2 signaling pathways[J]. Neuroscience, 2004,123(1):897-906.
  • 4Birght RB, Wadsworth S, Akakura BR, et al. A role for Schwann cells in the neuroregenerative effects of a non-immunosuppressive FK506 derivative JNJ460[J]. Neuroscience, 2004,124(6):351-366.
  • 5Anna P, Alberto P, Domingo R, et al. Persistence of tracer in the application site: a potential confounding factor in nerve regeneration studies[J]. J Neurosci Methods, 2003,127(2):105-110.
  • 6Jacobs WB, Fehlings MG. The molecular basis of neural regeneration[J]. Neurosurgery, 2003,53(4):943-948.
  • 7Olawale R, Sulaiman AND, Tessa G, et al. Transforming growth factor-beta and forskolin attenuate the adverse effects of long-term Schwann cell denervation on peripheral nerve regeneration in vivo[J]. Glia, 2002,37(3):206-218.
  • 8Johnson MD, Okediji E, Woodard A. Transforming growth factor-beta effects on meningioma cell proliferation and signal transduction pathways[J]. J Neurooncol, 2004,66(1-2):9-16.
  • 9David B, Parkinson, Ziping D, et al. Transforming growth factor-beta (TGF-β) mediateds Schwann cell death in vitro and in vivo: examination of c-Jun activation, interations with survival singnals, and the relationship of TGF-β-mediated death to Schwann cell differentiation[J]. Neuroscience, 2001,21(21):8572-8585.
  • 10Ryoke K, Ochi M, Iwata A, et al. A conditioning lesion promotes in vivo nerve regeneration in the contralateral sciatic nerve of rats[J]. Biochem Biophys Res Commun,2000,267(3):715-718.

共引文献8

同被引文献19

  • 1王岩峰,吕刚,李雷,韩壮,杨茂伟,黄涛.神经干细胞移植对大鼠脊髓损伤后胶质细胞源性神经营养因子与生长相关蛋白43基因表达的影响[J].中国修复重建外科杂志,2005,19(6):416-419. 被引量:22
  • 2侯巍,冯世庆,陈家童,王沛,周先虎,荆峰,郭世绂.Nogo抗体治疗脊髓损伤的实验研究[J].中华骨科杂志,2007,27(8):609-613. 被引量:8
  • 3Unni KK. Osteosareoma of bone. J Orthop Sci,1998,3 (5) :287- 294.
  • 4Chou AJ, Geller DS, Gorlick R. Therapy for osteosareoma:where do we go from here. Paediatr Drugs,2008,10(5 ) :315-327.
  • 5Bielack S,Carrle D ,Casali PG. Osteosarcoma:ESMO clinical rec- ommendations for diagnosis, treatment and follow-up. Ann Oncol, 2009,20(Suppl4) : 137-139.
  • 6Heidel JD, Liu JY, Yen Y, et al. Potent siRNA Inhibitors of Ribo- nucleotide Reductase Subunit RRM2 Reduce Cell Proliferation in vitro and in vivo. Clin Cancer Res,2007,13(7) :2207-2215.
  • 7Shankar P, Manjunath N, Lieberman J. The prospect of silencing disease using RNA interference. JAMA, 2005,293 ( 11 ) : 1367- 1373.
  • 8Takeshita F, Ochiya T. Therapeutic potential of RNA interference against cancer. Cancer Sci,2006,97 (8) :689-696.
  • 9Lin ZP,Belcourt MF,Cory JG,et al. Stable suppression of the R2 subunit of ribonucleotide reductase by R2-targeted short interfer- ence RNA sensitizes p.53 (-/-) HCT-116 colon cancer cells to DNA-damaging agents and ribonucleotide reductase inhibitors. J Biol Chem,2004,279(26) :27030-27038.
  • 10Duxbury MS,Ito H,Zinner MJ,et al. RNA interference targeting the M2. subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine. Oncogene, 2004,23(8) : 1539-1548.

引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部