神经调节因子―1Nrg1激活Nrg1―ErbB信号转导并促进小鼠脊髓损伤修复研究.docVIP

神经调节因子―1Nrg1激活Nrg1―ErbB信号转导并促进小鼠脊髓损伤修复研究 　　[摘要] 目的 研究神经调节蛋白-1（Nrg1）对脊髓损伤修复相关分子表达的影响并初步探讨其分子机制。 方法 将12只3个月龄C57BL/6雌性小鼠随机分成对照组和Nrg1给药组，每组6只，经过压迫性脊髓损伤后，通过鼠尾静脉注射分别连续给予DMSO溶剂和重组Nrg1β（rNrg1β）7 d，正常饲养6周后取其损伤部位脊髓样本进行蛋白免疫印迹（Western blot）检测Nrg1受体及相关分子蛋白的表达，比较两组间差异。 结果 与对照组比较，Nrg1给药组Nrg1受体ErbB4和Neu的磷酸化水平有所升高，其中ErbB4磷酸化水平显著升高（P0.01）；Nrg1给药组神经再生相关分子mTOR和Bcl-2表达显著升高（P0.05），而不利于损伤后修复的分子PTEN、GFAP和Bax的表达下降。 结论 通过外源性给予Nrg1激活其受体ErbB4和Neu，可升高小鼠脊髓损伤后神经再生相关分子mTOR磷酸化激活和Bcl-2蛋白水平，下调抑制脊髓损伤后修复相关分子PTEN、GFAP和Bax蛋白水平，这些作用可能是通过激活Erk信号通路实现的。 　　[关键词] 神经调节因子-1；脊髓损伤；修复；分子机制 　　[中图分类号] R363 [文献标识码] A [文章编号] 1674-4721（2016）04（b）-0004-04 　　[Abstract] Objective To study the effects of Neuregulin-1 （Nrg1） on the expression of molecules associated with repair of spinal cord injury in mice and to preliminarily explore the related molecular mechanism. Methods Twelve 3-month-old C57BL/6 female mice were evenly divided into control group and Nrg1 group，and each group contained 6 mice.Mice were administrated with either DMSO solvent or Nrg1β diluted in DMSO by tail vein injection for 7 consecutive days after spinal cord injury.Tissues within the injury site were collected for performing western blot to measure the expression level of the molecules involved after 6 weeks of routine feeding.The differences between two groups were compared. Results Compared with the control group，the phosphorylation levels of Nrg1 receptors ErbB4 and Neu were significantly elevated in the Nrg1 group （P0.01）.The protein levels of pmTOR and Bcl-2 were also significantly increased by Nrg1 when compared with the control group （P0.05） and the levels of PTEN，GFAP and Bax were apparently decreased in the Nrg1 group. Conclusion The phosphorylation levels of Nrg1 receptors ErbB4 and Neu can be increased by exogenous Nrg1.The protein levels of regeneration-promoting molecules after spinal cord injury，including pmTOR and Bcl-2，are elevated，whereas those of the regeneration-inhibiting molecules，including PTEN，GFAP and Bax，are reduced by