肿瘤坏死因子-α在大鼠脑缺血再灌注损伤中的作用机制

Mechanism of TNF-α in cerebral ischemia-reperfusion injury of rats

目的 探讨肿瘤坏死因 α(TNF α)在大鼠脑缺血再灌注损伤中的作用机制 ,尝试应用抗TNF α单抗进行缺血后的脑保护治疗。 方法 分别应用免疫组化方法和分光光度计比色法监测经大脑中动脉闭塞 2h后tor大鼠脑缺血再灌注不同时点TNF α的表达规律及髓过氧化物酶 (MPO)活性 ,并应用四氮唑红 (TTC)染色法测量再灌注 2 4h脑梗死灶体积。 结果 脑缺血再灌注后 2 4hTNF α表达和白细胞活性均达到高峰〔分别为 (3 7 86± 9 78)个和 (0 2 90± 0 0 71)U/ g湿组织 ;对照组分别为 (1 83± 1 41)个和 (0 0 16± 0 0 0 3 )U/ g湿组织〕 ,二者呈现同步变化。应用抗TNF α抗体可减少白细胞聚集〔治疗组为 (0 148± 0 0 3 3 )U/g湿组织〕和脑梗死灶体积〔手术组为 (15 8 7± 8 1)mm3,治疗组为 (86 3± 12 2 )mm3〕。 结论 TNF α通过炎性反应参与了缺血再灌注脑损伤 ,应用抗TNF

Objective Infiltration of leukocytes in the ischemic brain tissue suggests that the inflammation is involved in the reperfusion injury This experiment aims to study the mechanism of TNF α, an important inflammatory cytokine, in cerebral ischemia reperfusion injury, and to try using the anti TNF α antibody to protect the ischemic brain tissue Methods Wistar rats were randomly divided into control group, ischemia reperfusion group and therapy group. They were subjected to sham operation, middle cerebral artery occlusion(MCAO) and treatment with anti TNF α antibody 30 min after reperfusion, respectively Immunohistochemical technique was used to examine the expression of TNF α The myeloperoxidase(MPO) activity and the infarct volume were determined by spectrophotometry and TTC staining respectively Results Compared with ischemia reperfusion group, the infarct volume and the accumulation of leukocytes were obviously reduced in therapy group Both expressions of TNF α and the MPO activity reached peak 24 hours after cerebral ischemia reperfusion injury Conclusions The up regulation of TNF α in early period of reperfusion is involved in the mechanism of cerebral ischemia reperfusion injury The accumulation of leukocytes was an essential step in this mechanism The anti TNF α antibody can protect the brain tissue from ischemia