摘要
目的观察肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)在脑缺血/再灌注(ischemic/reperfusion,I/R)中的表达及核因子-κB(nuclear factor-κB,NF-κB)对其表达的调控作用。方法42只Wistar大鼠随机分为3组,用线栓法制作大鼠局灶性脑I/R模型。实验分为假手术(Sham)组;I/R组;吡咯烷二硫基甲酸酯(pyrroledithiocarbomate,PDTC,NF-κB抑制剂)+I/R组。各组动物均于脑缺血1 h再灌注,24 h后断头取脑,经氯化-2,3,5-三苯基四氮唑(2,3,5-triphenyl-tetrazolium chloride,TTC)染色后测脑梗死体积;采用凝胶电泳迁移率分析法(electrophoretic mobility shift assay,EMSA)测定脑组织NF-κB活性;应用酶联免疫吸附测定(enzymelinked immunosorbent assay,ELISA)试剂盒检测脑组织中TNF-α含量的变化;采用逆转录多聚酶链式反应(reverse transcriptase polymerase chain reaction,RT-PCR)方法观察脑组织中TNF-α表达的变化。结果脑缺血/再灌注后,大脑皮层及纹状体呈大面积梗死;脑组织NF-κB活性和TNF-α含量均显著增高,脑组织中TNF-α表达明显上调(P均<0.05)。PDTC可显著降低脑组织NF-κB活性和TNF-α含量,下调TNF-α的表达,减轻脑损伤,使大脑皮层及纹状体的梗死范围均有明显的缩小(P均<0.05)。结论NF-κB活化后可上调TNF-α的表达,参与脑缺血/再灌注后继发性炎症反应过程,抑制NF-κB活化可以减轻脑缺血/再灌注后脑组织的损伤。
Objective Inflammation mechanism is one of the injury factors of cerebral tissue after ischemia. The aim of the study was to investigate the expression of tumor necrosis factor- alpha（TNF-α） and its regulatory factor nuclear factor-κB（NF-κB） after cerebral ischemia/ reperfusiom. Methods Forty-two male Wistar rats were divided into three groups randomly. By using the suture model of focal cerebral ischemia and reperfusion, the effects of pyrroledithiocarbomate（PDTC）（the inhibitor of NF-κB） on the infarct size, the activity of NF- κB, the level and expression of TNF-α were observed in different brain regions of rats subjected tolh focal cerebral ischemia followed by 24 h reperfusion. Results The infarct size in different brain regions, the activity of NF-κB, the level and expression of TNF-α were attenuated by PDTC （all P 〈0.05）. Conclusion These results suggested that NF-κB could up-regulate the expression of TNF-α, which may be associated with the inflammatory reaction after cerebra lischemia/ reperfusion. PDTC could alleviate focal cerebra lischemia/reperfusion injury. The action may be associated with inhibition of NF-κB.
出处
《河北医科大学学报》
CAS
2006年第3期164-167,共4页
Journal of Hebei Medical University
