坐骨神经缺损后神经组织再生早期信号调控研究

目的:采用基因芯片技术结合信号传递调控网络(Signal-Flow)分析技术,探讨坐骨神经缺损近端神经组织早期分子信号调控机理。方法:SD大鼠坐骨神经缺损0h、0.5h、1h、3h、6h和9h后,取0.5cm近端神经组织进行mRNA芯片检测,进行差异基因的筛选和信号传递调控网络分析,并采用qRT-PCR对相关基因行表达趋势验证。结果:共筛选差异显著性基因2850个,抗凋亡相关因子和紧密连接蛋白等构成信号传递调控网络的核心部分。Birc2、Birc3和Tnfrsf1a早期上调抑制凋亡相关基因,紧密连接蛋白cldn14促进与其家族成员的结合。结论:抗凋亡因子和紧密连接蛋白可能是坐骨神经缺损后神经组织再生的内在早期调控分子,推测与神经组织损伤后内在的再生能力调控机制相关。

Analysis of molecular regulation in nerve tissues at early stages following sciatic nerve transection

Objective:To investigate the molecular mechanism of signal regulation in the proximal nerve after resection of the sciatic nerve by using gene microarray combined with Signal-Flow analysis.Methods:The proximal nerve tissues of 0.5cm were collected after the sciatic nerves of SD rats were transected at 0h,0.5h,1h,3h,6h and 9h,respectively.The dynamic gene regulatory network was inferred from time-series measurements of microarray data followed by screen of differential gene and pathway analysis.The mRNA expression was also further confirmed by qRT-PCR.Results:A total of 2850 differential genes were identified.Both anti-apoptosis factors and tight junction factors were the key elements in the gene regulatory network.Birc2,Birc3 and Tnfrsf1a were upregulated at the early stage,and inhibited the expression of apoptosis-related genes,whereas tight junction protein,cldn14,promoted the binding with other family members.Conclusion:Both anti-apoptosis factors and tight junction factors might be the early regulatory molecules involved in the nerve tissue regeneration,suggesting an association with the regulation of intrinsic growth capacity after nerve tissue injury.