目的 探讨SLIT-ROBO Rho GTPase激活蛋白2（srGAP2）在肌萎缩侧索硬化症(ALS)转基因小鼠脊髓运动神经元退变中的作用。方法  应用生物信息学分析srGAP2在人超氧化物歧化酶1（hSOD1）突变型ALS转基因小鼠脊髓中的表达变化。选取hSOD1G93A突变型ALS转基因小鼠进行实验验证，以同窝野生型（WT）小鼠为对照组，分为发病前期、早期、中期和晚期4组共36对，应用Real-time PCR、Western blotting和免疫荧光双标染色检测小鼠脊髓内srGAP2的表达变化及细胞定位。建立hSOD1G93A突变型NSC34运动神经元样细胞模型，体外实验检测srGAP2的表达变化，检测过表达srGAP2对hSOD1G93A突变型NSC34细胞活力的影响和细胞突起生长的影响。结果  生物信息学分析发现，srGAP2在hSOD1突变型ALS转基因小鼠脊髓中异常低表达。动物实验验证发现，与WT小鼠相比，在发病早期、中期和晚期hSOD1G93A突变型ALS转基因小鼠脊髓中srGAP2的mRNA水平和蛋白水平表达均降低。相较于WT小鼠，hSOD1G93A突变型ALS转基因小鼠脊髓前角srGAP2⁺/NeuN⁺双阳性细胞中srGAP2 积分吸光度（IA）值降低，srGAP2⁺/GFAP⁺双阳性细胞中srGAP2 IA值升高；与hSOD1WT NSC34细胞相比，hSOD1G93A突变型NSC34细胞中srGAP2的mRNA和蛋白表达均降低。过表达srGAP2可升高hSOD1G93A突变型NSC34细胞的活力，上调突起相关蛋白βⅢ-tubulin、生长相关联蛋白43（GAP43）的表达。结论  srGAP2低表达与ALS疾病进展密切相关，过表达srGAP2可促进突起生长，对ALS脊髓运动神经元具有保护作用

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) in spinal motor neuron degeneration in amyotrophic lateral sclerosis (ALS).   Methods   Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1) mutant ALS transgenic mice. hSOD1G93A mutant ALS transgenic mice were selected for animal experimental validation, with littermate wild type(WT) mice serving as the control group. A total of 36 pairs were divided into four groups, namely the pre-onset stage, early-onset stage, mid-onset stage, and late-onset stage. The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR, Western blotting and immunofluorescent double-label staining. The hSOD1G93A mutant NSC34 motor neuron-like cell model was established, and in vitro experiments were carried out to detect the changes in srGAP2 expression, and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.   Results  Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS  mice. Animal experiments verified that compared with the WT mice, the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset, mid-onset and late-onset stages. Compared with the WT mice, srGAP2 integral absorbance (IA) values in srGAP2⁺/NeuN⁺ double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower, srGAP2 IA values in srGAP2⁺/GFAP⁺ double-positive cells were higher; Compared with the hSOD1WT NSC34 cells, the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells. Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells, and up-regulated the expression level of synapse-related protein βⅢ-tubulin and growth associated protein 43（GAP43）.   Conclusion   Low expression of srGAP2 is closely associated with the progression of ALS, while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.