细胞因子对猴脑选择性超深低温断血流复苏缺血性脑保护的影响机制

The role of cytokines in the mechanism of cerebral protection after blood flow occlusion and resuscitation in selective monkey cerebral ultra-deep hypothermia

目的观察猴脑选择性超深低温断血流复苏实验前后血清中细胞因子的动态变化,了解脑缺血后选择性超深低温复苏对缺血性脑保护的炎性机制。方法健康恒河猴4只,先阻断双侧颈总动脉血流10分钟,然后建立闭胸式脑局部体外循环,行一侧颈内动脉冷灌注,同侧颈内静脉回流。60分钟后恢复脑血流,自然复苏。应用ELISA法统一测定实验前后猴血清中IL-2﹑IL-10﹑TNF-α﹑IFN-γ的浓度。结果4只恒河猴术后安全复苏并长期存活,术后头颅MRI检查正常,术后神经功能评分无异常。4种细胞因子在灌注结束后较术前均明显增高(P﹤0.05),24小时后恢复至术前水平,72小时测得值与术前无显著差异(P﹥0.05)。Spearman相关系数统计显示不同时间点促炎因子IL-2、TNF-α、IFN-γ与抑炎因子IL-10之间呈明显的正相关。结论猴脑选择性超深低温断血流复苏可引起抗炎细胞因子与促炎细胞因子一过性增高,其中抑炎因子IL-10的明显表达和促炎因子之间互相抑制,互相作用,促使细胞因子网络维持动态平衡,从而减轻机体炎性反应同时抑制了脑缺血后机体炎性反应所引起的脑组织损伤,发挥脑保护作用。

Objective To investigate the variations in serum interleukin-2（IL-2）, interleukin-10（IL-10）, tumor necrosis factor alpha（TNF-α）, INF-γ in monkey of resuscitation after selective cerebral ultra-deep hypothermia and blood flow occlusion. By means comprehention effects role of inflammatory in the mechanism of cerebral protection after cerebral ischemia selective cerebral ultra-deep hypothermiac blood flow occlusion and resuscitation. Methods For the four healthy maca mulattas, bilaferal common carotid artery blood flow were blocked for ten minutes before perfusion, then brain-lecal extractorporeal circulation was established by right Internal carotid artery ultraprofound hypothermic perfusion and homolateral internal jugular vein backflow. Brain blood flow was recovered from circulatory arrest of 60 minutes and the monkeys came back naturally. All the levels of these cytokines were measured by enzyme-linked immunosorbent assay（ELISA）. ResuIts Four monkey were succeeded resuscitation and lived up for ever. The function of neurological deficit scale and the MRI examinations of the monkeys were normal after operation.The levels of the four cytokines were significantly increased after perfusion （P 〈 0.05） ,descended to pre-operation levels after 24 huors, the levels 72 hours were not significantly difference than pre-operation levels. Spearman coefficient correlations between serum cytokine levels at different time. Conclusion The levels of pro-inflammatory and anti-inflammatory cytokines were significantly transient increased after monkey of resuscitation after selective cerebral ultra-deep hypothermia and blood flow occlusion. Because of pro-inflammatory and anti-inflammatory cytokines affect each other, the simultaneous increase of 2 cytokines can maintain the dynamic equilibrium of cytokine network, which is provides cerebral protection for inhibition inflammatory immune response to cause cerebral ischemi injury.