Investigation of Pathogenetic Mechanisms of Spinal Cord Insury using Bcl-2/Bax Transgenic and Knockout Mice

在本研究项目中，我们研究了原发损伤继发的神经细胞凋亡(程序性细胞死亡)在脊髓创伤损伤加重中的作用。为此，我们使用了在细胞凋亡调控中起重要作用的Bcl-2家族基因的转基因/敲除小鼠。我们首先利用气动冲击装置及其神经学评估系统建立了小鼠脊髓损伤模型。将该模型系统应用于Bc l-2转基因小鼠，获得了如下结果：1)创伤后神经功能恢复情况：Bc l-2转基因小鼠的神经功能恢复情况好于野生型小鼠。2)组织学定量评估显示，野生型小鼠的损伤体积(5.1±0.8×10~(-2)m l)与野生型小鼠(2.9±0.5×10~(-2)m l；这些结果表明，脊髓损伤后创伤性损伤的扩展在很大程度上受到Bcl-2家族蛋白的抗和促凋亡作用的影响。因此，我们认为Bcl2家族蛋白可作为预防脊髓损伤继发性损伤的重要治疗靶点。

In this research project, we investigated roles of neuronal cell apoptosis (programmed cell death) secondary to the primary injury in aggravation of traumatic lesion in the spinal cord. For this purpose, we used transgenic/knockout mice of Bcl-2 family genes which are important in regulation of cellular apoptosis. We first established a mouse model of spinal cord injury using a pneumatic impact device and its neurological evaluating system. Applying the model system on Bcl-2 transgenic mice, we obtained the following results:1) Post traumatic neurologic recovery showed a trend to be better in Bcl-2 transgenic mice than in wild-type mice2) Lesion volume assessed by histological quantative evaluation showed a statistically significant difference between wild-type mice (5.1 ± 0.8 x 10^<-2> ml) and Bcl-2 transgenic mice (2.9±0.5x10^<-2> ml).These results indicate that extension of traumatic lesion after a spinal cord injury is largely affected by the-anti- and pro-apoptotic effects of Bcl-2 family proteins. We therefore suggest that Bcl-2 family proteins can be important therapeutic targets in prevention of secondary damage in spinal cord injury.