3.2过氧化物歧化酶 目前在研究活性氧清除剂对实验性视神经炎的治疗中,对catalase研究得较多,而对另一种活性氧清除剂过氧化物歧化酶的研究相对较少。大概是因为其作用是歧化过氧化物生成H2O2, H2O2仍然是一种活性氧,因此并未从根本上起到解毒作用,所以过氧化物歧化酶疗效可能不如catalase确切。尽管如此,为研究锰-过氧化物歧化酶(Mn-SOD)及铜/锌-过氧化物歧化酶(Cu/Zn-SOD)对EAE中视神经的保护作用。Qi等[20]对EAE豚鼠及正常豚鼠视神经上的Mn-SOD、Cu/Zn-SOD及过氧化氢反应产物进行对照观察发现,在EAE豚鼠的视神经切片上,光镜下显示Mn-SOD阳性细胞分布在血管周围,电镜下显示只有Mn-SOD免疫金标记颗粒出现在视神经细胞的线粒体中,而Cu/Zn-SOD免疫金标记颗粒在EAE豚鼠及正常豚鼠视神经细胞的胞质及细胞核中都有分布。相对于正常豚鼠,在EAE豚鼠的视神经切片上,小胶质细胞/吞噬细胞中免疫金标记颗粒在星形胶质细胞中升高8倍,在小胶质细胞/吞噬细胞中升高13倍。增加的小胶质细胞/吞噬细胞中免疫金标记颗粒出现在过氧化氢反应产物附近,而没发现EAE豚鼠的视神经中有Cu/Zn-SOD免疫金标记颗粒的增加。此结果说明,在星形胶质细胞及小胶质细胞/吞噬细胞中Mn-SOD的增加在一定程度上保护了这些细胞免受氧化损伤,而在少突胶质细胞及轴突中Mn-SOD的低水平表达增加了它们对氧化损伤的易感性从而导致脱髓鞘作用。此后,Qi等[21]用腺病毒介导的核酶降低小鼠线粒体中的SOD2mRNA , 使其编码的Mn-SOD表达降低,ROS的水平上升,最终导致视神经变性。此实验进一步证实了超氧化物歧化酶在视神经保护中的作用。
4结语
目前活性氧清除剂对于实验性视神经炎的疗效已得到肯定。实验性变应性脑脊髓炎动物模型的建立为我们对于视神经炎发病学及治疗学的研究提供了可行性。但是因为现在的研究还只局限于动物模型,缺少临床实验依据,活性氧清除剂临床应用及其具体的给药时机、方式、剂量及药物疗效等还需进一步研究。
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