大鼠坐骨神经再生过程中许旺氏细胞的自噬作用

背景 Wallerian变性时髓鞘溃变碎片的清除对于神经的再生至关重要 ,但溃变碎片的清除机制一直没有彻底阐明 ,关于参与清除的细胞成分类型仍有很大争议. 目的 探讨大鼠坐骨神经再生过程中许旺氏细胞的自噬作用. 设计 完全随机自身对照研究. 地点和对象 本实验由第一军医大学解剖教研室、汕头大学医学院中心实验室和西南大学达拉斯医学中心精神病学部共同完成 ,研究对象为成年 Wistar大鼠 30只 ,雌雄各半 ,体质量 180- 250 g. 干预 横切大鼠坐骨神经制作 Wallerian变性模型 ,分别于造模后 0,0.5,1,1.5,2,3,4,5,7,10,15 d取远断端组织行电镜观察. 主要观察指标 电镜观察轴突和髓鞘的超微结构 ,Gomori染色后检查酸性磷酸酶活性. 结果 轴突在第 0.5天时从髓鞘脱离,溃变呈空泡状.第 2天开始髓鞘皱褶、断裂形成碎片,许旺氏细胞内见大的膜结合髓鞘碎片和许多散在小碎片,并与溶酶体融合形成自噬泡,呈酸性磷酸酶 (AcPase)阳性.第 4天时内膜区偶见幼稚细胞 ,1周后见大量幼稚细胞.第 7天后许旺氏细胞内自噬泡数量开始减少.实验全程偶见巨噬细胞 ,内有吞噬泡. 结论 大鼠坐骨神经再生过程中溃变髓鞘主要经许旺氏细胞自噬清除,许旺氏细胞脱分化为许旺氏细胞祖细胞后大量增殖分化参与神经再生过程.

The autophagic role of Schwann cell on regeneration of rat sciatic nerves

BACKGROUND:The removal of degenerated debris of myelin sheath during wallerian degeneration is very important for nerve regeneration,but the mechanism by which the debris is removed has not been completely clarified and there is still considerable controversies on the types of cells involved in the clearance process.OBJECTIVE:To investigate the autophagic role of Schwann cell on regeneration of rat sciatic nerves.DESIGN: Completely randomized animal experiment conducted in March 2003. SETTING AND PARTICIPANTS:Rats were bought from the Laboratory Animal Service Center of The First Military Medical University. Totally 30 adult Wistar rats were used, 15 males and 15 females,weighing 180- 250 g.INTERVENTION:Wallerian degeneration model was made by transecting the rat sciatic nerve.Samples from the distal stump were obtained 0,0.5,1,1.5,2,3,4,5,7,10,15 days after transaction,respectively,and ultrathin sections were prepared for examination with electron microscope.MAIN OUTCOME MEASURES:Ultrastructure of axon and myelin sheath were observed under electron microscope.Acid phosphatase(AcPase) activity was detected after Gomori staining.RESULTS:Axons start to separate from myelin sheath at day 0.5 after transection and degenerated quickly while displaying vacuole appearance.From day 2 onwards, myelin sheath creased and broke into fragments,large membrane bound myelin debris and many other small scattered ones appeared in Schwann cells and fused with lysosomes to form ACPase reaction positive autophagic vacuoles.Young cells were seen by chance at endoneural space and many of them appeared a week later.From day 7 onwards the number of autophagic vacuoles began to diminish.Macrophages were incidentally found all the time with autophagic vacuoles in it.CONCLUSION:The degenerating myelin debris were cleared mainly by autophagy of Schwann cells during regeneration of rat sciatic nerve.Schwann cells dedifferentiated to Schwann cell precursors,then proliferated and differentiated vastly to take part in the regeneration of nerves.