碱性成纤维细胞生长因子对兔全脑缺血再灌注损伤的保护作用

Protective effects of basic fibroblast growth factor against global cerebral ischemia/reperfuslon injury in rabbits

目的探讨碱性成纤维细胞生长因子(bFGF)对兔脑缺血再灌注损伤的保护作用。方法 24只大白兔,随机均分为假手术组、对照组和bFGF组,以“四血管阻断+体循环低血压”法制作兔心搏骤停后脑缺血再灌注损伤模型。bFGF组在缺血30min时将bFGF 30μg／kg经耳缘静脉注入,此后以10μg·kg-1·h-1微泵输入持续6 h,对照组仅应用等剂量的生理盐水,假手术组仅分离血管而不作其他处理。持续监测动脉血压、体温、心率,分别于夹闭血管前(T0)、开放血管即刻(T1)、开放血管后 0．5(T2)、1(T3)、3(T4)、6h(T5)测定血清神经元特异性烯醇化酶(NSE)、S-100B蛋白浓度,实验结束取脑组织测定脑水含量,在电镜下观察其超微结构。结果对照组、bFGF组T4 ,5时血清NSE、S-100B浓度高于假手术组(P<0．01);bFGF组T4 ,5时血清NSE、S-100B浓度低于对照组(P<0．05)。血清NSE与S- 100B浓度间的相关系数为0．736(P<0．01)。对照组和bFGF组脑水含量高于假手术组(P<0．01)。 bFGF组脑组织病理改变比对照组轻。结论 bFGF对兔脑缺血再灌注损伤有一定的保护作用。

Objective To investigate the effects of basic fibroblast growth factor （bFGF） on global cerebral ischemia/reperfusion （I/R） injury. Methods Twenty-four rabbits of both sexes aged 6 months weighing 2.2-3.0 kg were randomized into 3 groups （ n = 8 each） ： group Ⅰ sham operation; group Ⅱ I/R and group Ⅲ I/R ＋ bFGF. The animals were anesthetized with diazepam, halopefidol and fentanyl. The fight femoral artery was cannulated for BP monitoring and blood-letting. The animals were tracheotomized and mechanically ventilated （VT = 8 ml·kg^-1 , RR = 40 bpm, I ： E = 1 ： 2）. PETCO2 was maintained at 40 mm Hg. Global cerebral I/R was induced by ＂occlusion of four vessels ＋ hypotension＂ . Bilateral common carotid arteries and vertebral arteries were occluded for 30 min combined with hypotension, which was produced by blood-letting and maintained at 50%- 60% of the baseline level. The four vessels were then released for reperfusion and BP was returned to baseline level by retrieval of the removed blood. In sham operation group （ Ⅰ ） the four blood vessels were exposed but not occluded. In group m a loading dose of 30 μg·kg^-1 bFGF was given IV at the end of 30 min ischemia followed by bFGF infusion at 10 μg·kg^-1 . h^-1 for 6 h. In I/R group （ Ⅱ ） normal saline was given IV instead of bFGF. Blood samples were taken before I/R （T0, baseline） and at 0, 0.5, 1, 3, 6 h （T1-5） of reperfusion for determination of serum neuron specific enolase （NSE） and S-100B concentrations. At the end of the experiment the animals were killed and brains removed for determination of brain water content and microscopic examination. Results Serum NSE and S-100B concentrations in group Ⅱ and Ⅲ were significantly increased at T4-5 as compared to the baseline （T0） and were significantly higher at T4-5 than those in sham operation group （ Ⅰ ） . Serum NSE and S-100B concentrations were significantly lower in group m （I/R ＋ bFGF） than in group 1] （I/R）. Serum NSE and S-100B were positively correlated （ r = 0.736, P 〈 0.01 ）. Brain water content was significantly higher in group Ⅱ and Ⅲ than in sham operation group （ Ⅰ ） （P 〈 0.01 ）. The histo-pathological changes were milder in I/R ＋ bFGF group （ Ⅲ ） than in I/R group （ Ⅱ ）. Conclusion Basic fibroblast growth factor has protective effects against global cerebral I/R injury.