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巨噬细胞和视神经再生

http://www.cnophol.com 2009-12-10 11:24:43 中华眼科在线

    3  注射巨噬细胞以及巨噬细胞调理液

    3.1  注射巨噬细胞  Schwartz[32~33]研究小组的一系列研究提示移植激活的自体巨噬细胞可有助于克服CNS再生障碍,促进轴突的再生,有利于脊髓功能的改善和视神经的再生。血管的形成和雪旺氏细胞的渗入也更明显,这使层粘连蛋白增高,为轴突再生提供了一个合适的基质。Lazarov等[34]通过实验证实在横断处植入活化的巨噬细胞可促进RGC轴突长入远端的视神经,他们切断视神经,但保留血供和神经鞘的完整,巨噬细胞在体外孵育时用坐骨神经碎片活化后以混悬液植入横断处,7~8周后4Di-10ASP逆行标记发现有轴突再生。Yuqin等[35]将雄性大鼠在视乳头处钳压2 mm,5 s后制成视神经损伤模型。在其伤眼内损伤当日(A组)和3天后(B组)分别注射安慰剂PBS(n=4/每组)作为对照组,实验组在实验前7天(a组)和3天(b组),损伤当日(c组)和损伤后3天(d组),7天(e组)分别都注射酵母聚糖A(n=4/组)。提前7天注射酵母聚糖即可使局噬细胞水平大量增高并维持一至两个礼拜,而a组和b组未见能明显改善视神经再生水平,c组,d组平均能使受损侧神经生长4.7 mm,是a,b组的2倍,这提示并非巨噬细胞的数量决定了RGCs能否被刺激产生新的轴突和程度。d组是c组提高神经轴突再生水平的1.6倍(P=0.06),是B组的9倍(P<0.001)玻璃体内和视网膜内层表面可见ED-1阳性巨噬细胞。RGCs轴突和Somata的GAP-43表达明显上调,大量GAP-43阳性轴突越过受伤侧呈弧形沿视神经生长延长。E组未见损伤侧有轴突生长(与对照组比较,P<0.05)。体外实验[36]发现将切断后又重新连接的大鼠视神经浸浴在含有由坐骨神经孵育的巨噬细胞的溶液中,轴突能再生并通过断端。

    3.2  巨噬细胞调理液(macrophage conditional medium,MCM)   将生后2~3天Swagae-Dawley大鼠视网膜组织经胰蛋白酶消化后进行培养,并设对照组。结果培养在鼠尾胶原上的视网膜神经细胞(retinal Neurol,RN)生长良好,且部分细胞伸出突起培养1、3、5天,MCM促RN存活率分别为40.7%、39.9%和51.2%。故认为MCM能明显促进培养RN的存活和生长,表明MCM中存在某些促进RN存活的营养物质[37]。

    4  展望

    一些动物实验在一定程度上说明了适度激活的小胶质细胞/巨噬细胞有利于CNS损伤后结构和功能的修复。调控小胶质细胞/巨噬细胞的功能将是未来应用小胶质细胞/巨噬细胞作为一种治疗视神经损伤手段的方向。

    【参考文献】

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