重组人促红细胞生成素对脑缺血大鼠脑组织肿瘤坏死因子及白细胞介素6表达的影响  

Effects of recombinant human erythropoietin on expressions of tumor necrosis factor-alpha and interleukin-6 in rats with acute cerebral ischemia

作　　者：张金[1] 郭军红[1] 严澎[2] 王慧芳[1] 

机构地区：[1]山西医科大学第一附属医院神经内科,太原030001 [2]河南洛阳市中心医院神经内科

出　　处：《中华老年医学杂志》2013年第4期440-443,共4页Chinese Journal of Geriatrics

摘　　要：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a（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rhEP0治疗组（12只），手术后rhEPO治疗组在缺血2h后腹腔注射rhEPO5000U／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TNF-a、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-a阳性细胞数分别为（9．00±1．41）个、（27．83±2．48）个、（17．50±11．87）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-a、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〈O．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24h后的脑梗死体积；脑缺血后TNF-a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。Objective To investigate the effects of recombinant human erythropoietin（rhEPO） on expressions of tumon necrosis factor-alpha（TNF- a） and inter leukin-6 （IL-6） in rats after focal cerebral isehemia 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-a, 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 （36.67±2.40）% and （27.49 ± 1.47）%, respectively. Compared with the model group, the volume of infarction in rhEPO group wassignificantly reduced. Cells stained by immunohistochemistry showed that The numbers of TNF-a- positive cells in the 3 groups were 9.00 ±1.41, 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-a 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-a 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-a and IL-6.

关 键 词：脑缺血 红细胞生成素 重组 肿瘤坏死因子A 白细胞介素6 

分 类 号：R285.5[医药卫生—中药学]