碱性成纤维细胞生长因子保护兔全脑缺血再灌流损伤的研究

Mechanisms and neuro-protective effect of basic fibroblast growth factor on brain injury following global ischemia-reperfusion in rabbits

目的探讨碱性成纤维细胞生长因子(bFGF)对全脑缺血-再灌流损伤的保护作用及机制。方法24只大白兔随机均分为假手术组(A组)、对照组(B组)和bFGF组(C组);C组再灌流后输入bFGF持续6h,B组应用等量生理盐水,A组仅分离血管。分别测定缺血前、缺血30min及再灌流0.5、1、3、6h后血清神经元特异性烯醇化酶(NSE)、S100B蛋白及肿瘤坏死因子α(TNFα)、白细胞介素1(IL1)、白细胞介素8(IL8)的水平,并比较脑水含量和病理损害情况。结果B组和C组的NSE、S100B于再灌流1h开始增高,6h达峰值,再灌流3h、6h时B组明显高于C组;TNFα缺血30min后升高,再灌流后和IL1、IL8一起升高,6h达峰值。TNFα、IL1在3h、6h时C组较B组为低,IL8差异无显著性。B、C两组脑水含量差异无显著性,后者病理损害轻。结论bFGF对全脑缺血-再灌流损伤有保护作用,其机制与减少再灌流过程中炎症因子生成及介导的损伤有关。

Objective To study the mechanisms and neuroprective effects of basic fibroblast growth factor （bFGF） on brain injury following global ischemia-reperfusion. Methods Twenty-four rabbits were randomly divided into three groups. Brain injury following global ischemia-reperfusion was induced hy ligationof four vessels and systemic hypotension. bFGF was intravenously infused after reperfusion in bFGF group （Group C）. The same volume of normal saline was applied in control group （Group B）, only dissection of four vessels performed in sham group （Group A）. Blood samples were taken for determination of serum neuron specific enolase （ NSE）, S- 100B, tumor necrosis factor-α （TNF-α）, interleukin- 1 （ IL- 1）, interleukin-8 （IL-8） at baseline and 0.5, 1, 3, 6 h after reperfusion. Brain water was measured by dry-wet weight method and pathological features were examined. Results Serum NSE and S-100 were increased at 1 h after reperfusion and reached their peaks at 6 h after reperfusion, but were higher in group B than those in group C at 3 h and 6 h after reperfusion. TNF-α was increased in group B and group C after ischcmia, then continuously rose together with IL-1, IL-8 and reached their peaks at 6 h after reperfusion. TNF-α and IL-1 in group C were lower than those in group B at 3 h and 6 h. IL-8 and brain water were not different between group B and group C. There were milder pathological changes in group C. Conclusions bFGF protects brain from injury following global ischemia-reperfusion, by reducing production of inflammatory factors and antagonizing their adverse effects.