中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (23): 2117-2125.doi: 10.3969/j.issn.1673-5374.2013.23.001

• 原著:脑损伤修复保护与再生 •    下一篇

缺血性脑损伤中的自噬-溶酶体途径

  

  • 收稿日期:2013-04-26 修回日期:2013-07-08 出版日期:2013-08-15 发布日期:2013-08-15

The role of autophagic and lysosomal pathways in ischemic brain injury

Zhaohua Gu1, Yinyi Sun2, Kangyong Liu1, 2, Fen Wang3, Ting Zhang2, Qiang Li2, Liwei Shen4, Ling Zhou4, Liang Dong1, Nan Shi1, Qian Zhang1, Wei Zhang1, Meizhen Zhao1, Xiaojiang Sun2   

  1. 1 Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China
    2 Department of Neurology, the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China
    3 Department of Neurobiology, Suzhou University School of Medicine, Suzhou 215123, Jiangsu Province, China
    4 Department of Neurology, the Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China
  • Received:2013-04-26 Revised:2013-07-08 Online:2013-08-15 Published:2013-08-15
  • Contact: Xiaojiang Sun, Ph.D., Chief physician, Department of Neurology, the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China, sunxj155@sohu.com. Kangyong Liu, M.D., Ph.D., Associate chief physician, Department of Neurology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 234318, China; Department of Neurology, the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200233, China, liukangyong555@ yahoo.com.cn.
  • About author:Zhaohua Gu, Attending physician. Zhaohua Gu and Yinyi Sun contributed equally to this work.

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摘要：

研究表明，自噬参与脑缺血后神经细胞死亡。我们前期实验结果显示用雷帕霉素诱导自噬可降低细胞凋亡率，而用自噬抑制剂3-MA抑制自噬则细胞凋亡率显著增加。本次实验中以线栓法建立大鼠缺血性脑损伤模型，透射电镜发现大鼠大脑皮质中自噬小体和自噬溶酶体在缺血性脑损伤后4h在神经元内显著地积聚，但随着时间的延长逐渐减少；蛋白免疫印迹分析发现，缺血性脑损伤后脑组织内自噬的2个标记物微管相关蛋白轻链3和组织蛋白酶B在脑缺血损伤后4h开始内大幅上调，但并非随时间的延长持续性上调；共聚焦显微镜观察自噬主要发生于神经细胞元中（呈微管相关蛋白轻链3阳性）。尾静脉注射雷帕霉素促进脑缺血大鼠脑组织中自噬的发生及微管相关蛋白轻链3和组织蛋白酶B的表达，而注射自噬抑制剂3-MA能明显降低脑缺血大鼠脑组织中微管相关蛋白轻链3-Ⅱ和cathepsin B的表达。结果证实在缺血性脑损伤后自噬-溶酶体途径持续地活化，缺血性脑损伤发生后可通过上调细胞的自噬或者抑制自噬，消除细胞中的异常成分，保持细胞中物质和能量动态平衡，而干预自噬的药物能够影响脑损伤的治疗。