TNF-α拮抗剂(Etanercept)治疗脊髓损伤作用机制的实验研究

Experimental study on mechanism of tumor necrosis factor-alpha antagonist (Etanercept) for acute spinal cord injury

目的探讨TNF-α拮抗剂Etanercept(依那西普)对继发性脊髓损伤的治疗作用和可能机制。方法建立大鼠脊髓挫伤模型,损伤后1 h对大鼠行腹腔注射5 mg/kg Etanercept或生理盐水(损伤对照组);假手术组(20只大鼠)仅行椎板切除术而无脊髓损伤,1 h后给予腹腔注射1 ml生理盐水。结果在脊髓损伤急性期(12 h、1 d、3 d),Etanercept治疗组TNF-α的蛋白表达强度明显弱于损伤对照组。与对照组相比,Etanercept治疗组TNFR1的表达在损伤后6、12 h均下降,TNFR2仅在损伤后6 h下降。损伤对照组大鼠在脊髓损伤后后肢运动功能明显受限,而Etanercept治疗组大鼠在脊髓损伤后2、4、8周,后肢BBB评分显著升高。结论 Etanercept可能通过抑制TNF-α/TNFR通路,减轻了脱髓鞘变性,促进了运动功能的恢复。

Objective To investigate the contribution of etanercept to the pathological cascade in spinal cord injury （SCI） and its possible suppression of tumor necrosis factor receptors. Methods SCI contusion models were reproduced applying a 90 grams weight over the spinal cord exposed at T10. 5 mg/kg Etanercept or saline （control） was administered by intraperitoneal injection 1 hour after thoracic spinal cord injury in rats; rats subjected to laminectomy, but with no spinal cord injury sustained, served as the sham-operated group （n =20）. Results The relative expression of TNF-α expressionsin the etanercept-treated group were weaker than those in the control animals, especially in the acute phase （12 hours, 1 day, and 3 days） after spinal cord injury. TNFR1 expression was significantly lower in the treatment group at 6 and 12 hours post-injury compared to the controls. TNFR2 expression was also reduced in the etanercept-treated group at 6 hours compared to controls. Rats sustaining spinal cord injury had significant motor disturbances in the hind limb. Etanereept administration significantly increased the BBB locomotor score at 2, 4, and 8 weeks after the cord injury. Conclusion Our study suggested that suppression of TNF-α/TNFR pathway in the acute phase of cord injury by etanereept administration eottld possibly contribute to inhibition of demyelation and promote better recovery of locomotor function.