坐骨神经结扎大鼠脊髓神经元凋亡与痛敏的关系

RELATION BETWEEN SPINAL NEURONAL APOPTOSIS AND NEUROPATHIC PAIN IN RATS FOLLOWING SCIATIC NERVE LIGATION

目的:探讨坐骨神经结扎大鼠脊髓神经元凋亡与痛敏的关系。方法:成年雄性W istar大鼠50只,采用坐骨神经中段结扎模型,于术前、术后6h、1、3、7及14d分别测定抬足和甩尾潜伏期。应用免疫组织化学方法和图象分析系统检测脊髓中肿瘤坏死因子α(tumor necrosis factor-,αTNF-α)和白细胞介素6(interleukin-6,IL-6)的表达,采用TUNEL法观察脊髓神经元凋亡,同时用HE及尼氏染色法观察脊髓的病理改变。结果:坐骨神经结扎后6h可诱发出大鼠机械性触诱发痛和热痛觉过敏;TNF-α于结扎后6h开始表达,1d达高峰,并于术后14d恢复到基线水平;IL-6于结扎后1d开始表达,术后3d达峰值并持续到术后7d,而后慢慢降低;术后6h脊髓中开始有少量凋亡神经元出现,凋亡指数于术后1d开始迅速增加,术后3d达峰值。结论:结扎坐骨神经可诱发神经源性痛,并导致脊髓神经元的凋亡,其机制可能与促炎性细胞因子TNF-α和IL-6的过度表达有关。

Objective：To investigate the relation between spinal neuronal apoptosis and CCI-induced neuropathic pain. Methods： Thirty-six healthy adult male Wistar rats receiving sciatic nerve ligation were tested for paw and tail withdrawal latency at -1 day, 6 h, 1,3, 7 and 14 days after surgery, respectively. Then rats were sacrificed, and spinal cords were removed for apoptotic, immunohistochemical and histochemical analyses at the corresponding time points. Results： Mechanical allodynia and thermal hyperalgesia developed at 6 h after sciatic nerve ligation; TNF-α ,IL-6 and neuronal apoptosis were first detected in spinal cord 6 h and i d after injury and peaked at i d, 3 d and 7d respectively. Conclusion： Our findings indicated that sciatic nerve ligation can lead to spinal neuronal apoptosis, which may be associated with the overexpression of TNF-α and IL-6 in the spine cord, a possible mechanism for neuropathic pain.