促红细胞生成素对大鼠坐骨神经损伤后炎性反应和细胞凋亡的影响

The impact of erythropoietin on inflammalion and neuronal apoptosis after sciatic nerve injury in rats

目的 探讨促红细胞生成素（EPO）对大鼠坐骨神经损伤后炎性反应和细胞凋亡的影响及其作用机制,为周围神经损伤的临床治疗提供实验依据.方法 雌性SD大鼠36只,制备大鼠左侧坐骨神经缺损模型,随机分为3组,即EPO组、神经生长因子（NGF）组和生理盐水（NS）组.EPO组、NGF组和NS组分别于术后立即及每日腹腔注射FPO、NGF和NS.术后7、14 d,HE染色光镜下观察L5背根神经节细胞形态变化；应用RT-PCR检测损伤近、远端坐骨神经IL-6和TNF-α mRNA的表达；以TUNEL法检测L5背根神经节细胞凋亡.结果 术后7、14 d,EPO组近、远端坐骨神经IL-6mRNA表达低于NS组,差异有统计学意义（P＜0.01）；EPO组远端坐骨神经IL-6 mRNA表达低于NGF组,差异有统计学意义（P＜0.01）.术后7d,EPO组近、远端坐骨神经TNF-α mRNA表达低于NS组和NGF组,差异有统计学意义（P＜0.01）；术后14 d,EPO组远端坐骨神经TNF-α mRNA表达低于NS组,差异有统计学意义（P＜0.05）.术后7、14 d,EPO组凋亡细胞数低于NS组,差异有统计学意义（P＜0.01）；术后14 d,EPO组凋亡细胞数低于NGF组,差异有统计学意义（P＜0.05）.结论 EPO可能通过减少致炎因子IL-6和TNF-α释放,减轻炎性反应,抑制细胞凋亡,对大鼠坐骨神经损伤发挥保护作用.

Objective To explore the effect of erythropoietin on inflammation, neuronal apoptosis and the possible mechanism after sciatic nerve injury in rats and provide experimental basis for clinical treatment of peripheral nerve injury.Methods Left sciatic nerve defect was created in 36 female Sprngue-Dawley rats which were divided into three groups：normal saline（NS）group,erythropoietin（EPO）group and nerve growth factor（NGF）group.NS,EPO and NGF were administered by intraperitoneal injection in the NS group,EPO group and NGF group,respectively.At 7 and 14 days after the operation,the morphological change of L5 dorsal root ganglion neurons was observed by light microscope.The expression of IL-6 and TNF-α mRNA of both proximal and distal stumps were quantified using RT-PCR.The neuronal apoptosis of L5 dorsal root ganglion was assessed by TUNEL.Results At 7 and 14 days after the operation,the expression of IL-6 mRNA of both proximal and distal stumps in EPO group was less than that in the NS group（P 〈 0.01）.The expression of IL-6 mRNA of distal stumps in EPO group was less than that in the NGF group（P 〈 0.01）.The expression of TNF-α mRNA of both proximal and distal stumps in EPO group was less than that in the NS and NGF groups（P 〈0.01）7 days postoperatively.The expression of TNF-α mRNA of distal stumps in EPO group was less than that in the NS group（P 〈0.05）14 days postoperatively.At 7 and 14 days after the operation,neuronal apoptosis in EPO treatment group was lower than NS treatment group（P 〈 0.01）,while neuronal apoptosis in EPO treatment group was lower than NGF treatment group（P 〈 0.05）14 days postoperatively.Conclusion EPO can attenuate injury-induced inflammation and inhibit dorsal root ganglion apoptosis,which may provide protective effect for sciatic nerve injury in rats.