粒细胞集落刺激因子对新生大鼠缺氧缺血性脑损伤后脑组织VEGF及bax的影响

目的探讨粒细胞集落刺激因子(G-CSF)对新生大鼠缺氧缺血性脑损伤(HIBD)后脑组织血管内皮生长因子(VEGF)及bax的影响。方法7d龄Wistar大鼠168只随机分为3组:假手术对照组(A组),HIBD组(B组),HIBD+G-CSF治疗组(C组)。各组根据处死时间不同又分为7个亚组:6,12,24,48,72h组,5d组,7d组。建立HIBD模型,C组在缺氧缺血后即刻给予G-CSF(100μg/kg)。各组分别于HIBD后不同时间点取脑组织,A组也在相应时间点取脑组织,用免疫组织化学法检测各组脑组织中VEGF及bax的表达。结果A组脑组织各时间点均无明显VEGF和bax阳性表达;B组各时间点脑组织均可见VEGF和bax阳性表达,24～48h为表达高峰期,以后逐渐下降;C组各时间点脑组织VEGF阳性表达较A组和B组均明显增高,bax阳性表达较A组增高,但较B组均明显降低。同一时间点3组VEGF阳性表达相比差异均有统计学意义(P<0.01)。结论①新生大鼠HIBD后各时间点脑组织VEGF表达增加,可能与HIBD后神经组织自身修复能力有关;bax表达亦增加,与神经细胞凋亡有关。②G-CSF治疗后可明显增加新生大鼠HIBD后脑组织VEGF表达,降低bax表达,从而促进脑组织缺氧缺血损伤后结构和功能上的恢复。

Effect of G-CSF on VEGF and bax in brain tissue after HIBD in neonatal rats

Objective To probe the effect of G-CSF on VEGF and bax in brain tissue after HIBD in neonatal rats.MethodsA total of 168 seven-day Wistar rats were randomly divided into three groups(n=56 in each group):A group(sham operation control group),B group(HIBD group),C group(HIBD+G-CSF treatment group).Then each group was divided into seven sub-groups(n=8 in each subgroup)based on different time points after HIBD(6,12,24,48,72 hours,5,7 days).HIBD model was established.Rats in C group were subcutaneously given G-CSF 100 μg/kg body weight for 5 days after HIBD.Animals were sacrificed at different time points,the expression of VEGF and bax in brain tissue were detected with immunohistochemistry.ResultsVEGF-positive cell and bax-positive cell in cerebral cortex of B group on at each time points after operation were increased compared with A group,VEGF-positive cell in cerebral cortex of C group were increased notably compared with A group and B group,Bax-positive cell of C group were increased compared with A group,but decreased significantly compared with B group,the comparison of three groups on the same time point had statistical differences(P<0.01).Conclusion①The expression of VEGF in cerebral cortex of neonatal rats with HIBD increased,which contributes to the restoration of nerve tissue after HIBD.The expression of Bax increased after HIBD,which is involved in cell apoptosis.②G-CSF treatment can increase the expression of VEGF and decrease the expression of Bax in cerebral cortex after HIBD,and protect the damaged brain.