Objective To investigate the effects of recombinant human erythropoietin(rhEPO)on expressions of tumon necrosis factor-alpha(TNF-α) and inter leukin-6(IL-6) in rats after focal cerebral ischemia and to explore its neuroprotective mechanism.Methods A total of 36 healthy male SD rats were randomly divided into sham-operated group (n=12),model group (n=12) and rhEPO treatment group (n=12).The suture method to make permanent middle cerebral artery occlusion model was adopted.rhEPO treatment group was injected with rhEPO 5000 U/kg intraperitoneally after 2 h of ischemia,whereas model group and sham-operated group were given identical saline at the same time.All rats were decapitated after 24 h of ischemia.6 rats were randomly selected in each group and the infarct volume of groups were measured by Triphenyl tetrazolium chloride (TTC)staining method.The expressions of TNF-α,IL-6 in other rats were detected by immunohistochemistry.Results No infarction was found in sham-operated group.Percentage of infarct volume in model group and rhEPO group were (36.672.40)％ and (27.49± 1.47)％,respectively.Compared with the model group,the volume of infarction in rhEPO group was significantly reduced.Cells stained by immunohistochemistry showed that The numbers of TNF-α-positive cells in the 3 groups were 9.001.41,27.83±2.48,17.50±1.87 and IL 6 positive cells were 8.94±2.31,20.33±3.53,14.83±1.70,respectively.Compared with sham operated group,the expressions of TNF-α and IL 6 in model group were significantly increased (q=16.1,19.6,P＜0.01).Compared with the model group,the expressions of TNF α and IL-6 in rhEPO group were significantly decreased (q=8.19,3.44,all P＜0.01).Conclusions rhEPO can decrease the infarct volume in SD rats after acute focal cerebral ischemic injure.rhEPO might exert its neuroprotective effect by reducing the expressions of TNF α and IL-6.%目的 观察重组人促红细胞生成素(rhEPO)对大鼠永久性脑缺血脑组织中肿瘤坏死因子α(TNF-a)、白细胞介素6(IL-6)表达的影响,探讨其对脑缺血的保护作用及作用机制. 方法 采用血管内线栓法制备大鼠永久性局灶性脑缺血(pMCAO)模型.健康雄性SD大鼠36只,随机分为假手术组(12只),模型组(12只),手术后rhEPO治疗组(12只),手术后rhEPO治疗组在缺血2h后腹腔注射rhEPO 5000 U/kg,模型组和假手术组在缺血2h后腹腔内注射等量的生理盐水.各组随机选6只用于2,3,5-氯化三苯基四氮唑(TTC)法测量脑梗死体积,另6只用于免疫组织化学方法测定TNFα、IL-6的表达. 结果 TTC测定脑梗死体积显示,假手术组、模型组和rhEPO治疗组脑梗死体积百分比分别为0、(36.67±2.40)％和(27.49±1.47)％(F=823.50,P＜0.01),与模型组及假手术组比较,rhEPO治疗组脑梗死体积明显减小(q=7.98、45.81,均P＜0.01).免疫组织化学检测结果显示,假手术组、模型组和rhEPO治疗组脑组织TNF-α阳性细胞数分别为(9.00±1.41)个、(27.83±2.48)个、(17.50±1.87)个,IL-6阳性细胞数分别为(8.94±2.31)个、(20.33±3.53)个、(14.83±1.70)个；模型组与假手术组比较,TNF-α、IL-6表达均有所增加(q=16.1、19.6,均P＜0.01),而rhEPO治疗组较模型组TNF-a和IL-6的表达有所下降(q=8.19、3.44,均P＜0.01). 结论 在大鼠缺血2h后腹腔内注射rhEPO可以缩小大鼠脑缺血24 h后的脑梗死体积；脑缺血后TNF-α及IL-6的表达升高,rhEPO可能通过降低TNF-a及IL-6的活性来发挥其神经保护作用.
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