3 GDNF临床应用需要解决的问题
大量的实验证实GDNF对于SCI有着很强的修复作用,可以保护神经元细胞,促进轴突的再生,但目前GDNF治疗SCI仍处于临床前的实验阶段,要应用于临床应用还需要解决以下问题:(1)疗效问题,SCI目前临床上仍没有确切的治疗方法,所有的方法都停留在实验阶段,GDNF促进SCI修复的作用,体外实验和动物实验都已经证实,但哺乳动物,甚至人体内实验目前尚未有实验证实,这需要有进一步的实验来证实。单独使用GDNF治疗SCI疗效有限,联合其它方法更有临床应用前景;(2)安全问题,目前使用的外源性GDNF是重组的GDNF,作为治疗用药,其药代动力学、稳定性、溶解度、纯度等问题以及可能机体带来的副作用仍不确定,近期有实验表明外源性的GDNF,由于纯度等问题,可以使机体产生抗体,影响疗效,甚至会交叉反应,对抗自体生成的内源性的GDNF,对机体产生不良的影响[26];(3)剂量问题,GDNF浓度与轴突再生的做用非线性关系,在高浓度和低浓度时GDNF作用较弱[15]。甚至有研究表明超出剂量范围使用GDNF反而阻止外周损伤神经元轴突的生长[30]。
GDNF促进SCI修复作用已经得到很多实验的证实,很多学者也采取了不同的途径对GDNF在治疗脊髓方面探索,取得了不少成果,但由于SCI的修复因素很多,单一使用GDNF无法完成SCI的完全修复,目前GDNF对SCI修复的研究还处于实验阶段。GDNF联合应用细胞移植、基因治疗、其他神经营养因子等方法治疗SCI将是今后研究SCI治疗的主要方向之一。
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