促红细胞生成素对颅脑创伤后炎性反应和细胞凋亡的影响

Effect of recombinant human erythropoietin on expression of inflammatory reaction and neutral apoptosis after traumatic brain injury

目的 探讨重组人促红细胞生成素（rhEPO）对大鼠创伤性脑损伤后（TBI）脑组织核因子NF—KB的表达、下游炎性因子水平及皮层神经细胞凋亡的调控作用。方法72只Wistar大鼠随机分成对照组、TBI组、TBI＋rhEPO组，后两组再分为脑损伤后1d、3d、7d亚组，应用EMSA法检测挫伤灶周围脑组织NF—KB结合活性、ELISA法检测炎性因子TNF-α、IL-6水平、干湿比重法检测脑组织水含量、TUNEL法检测皮层神经细胞凋亡。结果TBI后脑组织中NF—KB结合活性、炎性因子水平持续升高；伤后脑水肿明显；TUNEL阳性细胞显著增多。给予rhEPO治疗后，脑组织NF—KB结合活性、TNF-α、IL-6水平、伤侧脑组织水肿程度及神经细胞凋亡均比TBI组降低（P〈0．01）。结论rhEPO能够抑制TBI后脑组织NF—KB的结合活性、降低下游炎性因子的表达和脑水肿程度、减少神经细胞凋亡，明显减轻继发性脑损害。

Objective To investigate the role of rhEPO in regulating expression of nuclear factor - kappaB （NF- kB）,proinflammatory cytokines and neural apoptosis in the injured brain following traumatic brain injury. Methods A total of 72 Wistar rats were randomly divided into control group, trauma group and rhEPO treatment group. TBI group and rhEPO group sacrificed at days 1, 3 and 7 post injury respectively. Activity of NF - KB in the brain tissues were detected by using EMSA and levels of TNF - a and IL - 6 by ELISA. The water content of the injured brain was measured by dry -wet weight method. Furthermore, apoptosis in the cortical contusion was estimated by TUNEL method. Result The result showed a persistent up - regulation of NF - KB binding activity, expression of TNF - a ,IL -6 in the area surrounding the injuried brain and significant brain edema The TUNEL positive cells significantly increased. The level of NF - kB binding activity and inflammatory factors expression, the water content of the injury brain and apoptosis can be significantly decreased by administration of rhEPO （ P 〈 0. 01 ）. Conclusion rhEPO administration can inhibit the binding activity of the NF - kB, down - regulate the expression of the inflammatory factors, alleviate the brain edema and apoptosis and decrease the secondary brain injury after TBI.