Akt/XIAP信号通路在脊髓损伤后抑制神经细胞凋亡

Akt/XIAP Signaling Pathway Inhibits Neuronal Apoptosis After Spinal Cord Injury

为探讨Akt/XIAP信号通路在脊髓损伤后神经细胞凋亡调节中的作用,本研究将90只SD大鼠使用随机数表法分为3组:对照组、假手术组、脊髓损伤组,每组30只。对照组的SD大鼠不做任何处理;假手术组的大鼠不打击脊髓,仅对其进行推板切除术,并缝合伤口;对于脊髓损伤组则根据改良的Allen’s法建立大鼠脊髓损伤模型。对3组大鼠进行HE染色和免疫组织化学染色,检测Akt/XIAP信号通路下游因子GSK-3β和凋亡相关因子caspase12、Bcl-2的表达水平,并利用SPSS25.0统计软件进行分析。结果显示,损伤4 h后的脊髓损伤组神经细胞出现胞内水肿,毛细血管扩张,灰质结构损坏。且损伤12 h、24 h和72 h后,上述现象逐渐加深,但168 h与72 h无明显变化。对照组的表达量显著低于脊髓损伤组,且随着时间的增加,在第7天时达到峰值,随后则开始缓慢下降。对照组可见胞浆呈现棕黄色颗粒的P-Akt和P-XIAP的阳性表达,但只有少量存在。而假手术组的P-Akt和P-XIAP的阳性表达则显著性高于对照组(p<0.05),在脊髓损伤4 h时即可见阳性表达,12 h后阳性表达量达到最高值,此后慢慢减少。脊髓损伤组各个时间点的P-Akt和P-XIAP的阳性表达量均较少,但阳性表达仍在12 h时达到最高值(p<0.05)。说明脊髓损伤后脊髓神经元内Akt/XIAP信号通路被激活,此通路可能具有抑制神经细胞凋亡,从而起到神经保护的作用。本研究结果可为临床提供可参考的理论依据。

To investigate the role of Akt/XIAP signaling pathway in the regulation of neuronal apoptosis after spinal cord injury.90 SD rats were randomly divided into 3 groups:control group,sham operation group,spinal cord injury group with 30 rats in each group.The rats in the control group did not do any treatment;the rats in the sham operation group did not hit the spinal cord,only performed push plate resection,and then sutured the wound.In the spinal cord injury group,the spinal cord injury model was established according to the modified Allen’s method.The three groups were stained with HE and immunohistochemistry.The expression of GSK-3β,caspase12 and Bcl-2,and the downstream factors of Akt/XIAP signal pathway were detected and analyzed with spss25.0 statistical software.The results showed that after 4 hours of injury,the nerve cells in the spinal cord injury group showed intracellular edema,capillary dilation,gray matter structure damage and even death.After 12 hours,24 hours and 72 hours,the above phenomenon gradually deepened,and there was no significant change at 168 hours and 72 hours.The expression of P-Akt and P-XIAP in the control group was significantly lower than that in the spinal cord injury group,and with the increase of time,they reached the"peak"on the 7 thday,and then began to decline slowly.However,the positive expression of P-Akt and P-XIAP in the sham operation group was significantly higher than that in the control group(p<0.05),and the positive expression could be seen at 4 h after spinal cord injury.The positive expression reached the highest value 12 hours later,and then decreased slowly.The positive expression of P-Akt and P-XIAP in spinal cord injury group was less,but the positive expression still reached its highest value at 12 h(p<0.05).After spinal cord injury,Akt/XIAP signaling pathway is activated in spinal cord neurons,which may inhibit the apoptosis of neurons and play a neuroprotective role.The results of this study can provide a theoretical basis for clinical reference.