目的 探讨细胞凋亡信号调节蛋白1(ASK1)在炎症因子介导的大鼠脊髓损伤(SCI)中的作用.方法 采用大鼠脊髓夹伤模型,48只大鼠分为假手术组(Sham组)、生理盐水组(Saline组)及炎症因子组(Cytokine组),用Western blot法检测ASK1和磷酸化的ASK1 (pASK1)的表达,用BBB评分及Grid Walking法检测后肢行为学变化,用体感诱发电位(SEP)及运动诱发电位(MEP)检测电生理变化.结果 SCI后1周各组ASK1 mRNA及蛋白水平的表达无明显变化,Cytokine组pASK1的表达较Saline组显著上调(P=0.002);SCI后3、4周时,Cytokine组BBB评分较Saline组明显下降(P=0.000、0.000);SCI后4周,与Saline组相比,Cytokine组大鼠后肢踏空率增加(P=0.032),SEP及MEP潜伏期延长(P=0.043、0.045),波峰值无显著变化(P=0.889、0.434).结论 炎症细胞因子可导致大鼠SCI后后肢运动功能障碍加重,机制可能与ASK1磷酸化水平升高有关.%Objective To explore the role of apoptosis signal regulating kinase 1(ASK1) in inflammatory mediated secondary injury after spinal cord injury(SCI) in rats.Methods The rat contusion SCI model was used.Forty-eight rats were randomly divided into the sham operation group(Sham),normal saline(Saline group) and inflammatory factors group (Cytokine group) respectively.The expressions of ASK1 and phosphorylated ASK1(pASK1) were detected by using Western blot.The Basso Beattie Bresnahan (BBB) scores and Grid Walking method were performed to assess the behavior changes of injured rat hindlimbs.Somatosensory evoked potential(SEP) and motor evoked potential(MEP) were used to examine the electrophysiological change.Results The expression levels of ASK1 mRNA and protein had no obvious change at 1 week after SCI;the pASK1 expression level in the Cytokine group was significantly up-regulated compared with the Saline group(P=0.002);the BBB scores at 3 or 4 weeks after SCI in the Cytokine group was significantly decreased compared with the Saline group (P =0.000,P =0.000);the hindlimbs missed step rate at 4 weeks following SCI in the Cytokine group was increased compared with the Saline group (P =0.032);the latent period of SEP and MEP in the Cytokine group was prolonged(P =0.043,P =0.045),while the wave peak value had no obvious changed (P =0.889,P=0.434).Conclusion Inflammatory cytokines may lead the hindlimbs movement dysfunction to be aggravated after SCI in rat,its mechanism may be related with the phosphorylation elevation of ASK1.
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