不同剂量的rhG-CSF对新生大鼠缺氧缺血性脑损伤后脑组织VEGF的影响

Effects of different doses of rhG-CSF on VEGF in brain tissue after hypoxic-ischemic brain damage in neonatal rats

目的探讨不同剂量的rhG-CSF对新生大鼠缺氧缺血性脑损伤后脑组织VEGF的影响。方法7日龄Wistar大鼠96只随机分为四组:缺氧缺血性脑损伤(HIBD)模型组,rhG-CSF小剂量组(60μg/kg),中剂量组(100μg/kg),大剂量组(200μg/kg),每组各24只。每组根据处死时间不同又分为三个亚组:24h组,48h组,72h组,每亚组各8只。各组均建立新生大鼠缺氧缺血性脑损伤模型,治疗组分别在缺氧缺血后即刻给予rhG-CSF60μg/kg,100μg/kg,200μg/kg颈部皮下注射,并连用3d。各组于不同时间点取脑组织,用免疫组化法检测脑组织中VEGF的表达。结果与HIBD模型组各时间点相比,rhG-CSF各剂量组脑组织VEGF表达均明显增加,差异均有统计学意义(P<0.01);同一时间点rhG-CSF各剂量组间VEGF表达差异均无统计学意义(P>0.05),但小剂量组各时间点脑组织外观两侧基本对称,而中剂量组及大剂量组缺氧缺血侧脑组织出现水肿,大剂量组较明显。结论rhG-CSF治疗可明显增加脑组织VEGF的表达,有利于脑组织结构和功能的恢复,60μg/kg为较合适的剂量。

Objective To explore the effect of different doses of recombinant human granulocyte colony-stimulating factor（rhG-CSF） on VEGF in brain tissue after hypoxic-ischemic brain damage in neonatal rats. Methods A total of 96 seven-day-old Wistar rats were randomized into four groups （n = 24 in each group） ： hypoxic-ischemic brain damage （HIBD）group, low dose rhG-CSF group, medium dose rhG-CSF group,high dose rhG-CSF group. Then each group was divided into three subgroups（ n = 8 in each subgroup）based on different time points after HIBD （24 h ,48 h,72 h）. HIBD model was established. The rats were subcutaneously given rhG-CSF 60,100, 200 μg/kg body weigh for 3 d after HIBD in rhG-CSF groups, respectively. Rats were sacrificed at different time points, and then the ex- pression of VEGF in brain tissue was detected with immunohistochemistry. Results Expression of VEGF in brain tissue at different time points in rhG-CSF groups increased significantly compared with HIBD group （ P 〈 0.01 ）, but there was no statistical difference be- tween rhG-CSF groups at the same time point（ P 〉 0.05）. The hemisphere of bilateral brain was symmetrical in appearance in low dose group, while edema occurred in HIBD-side brain in medium and high dose groups. Conclusion The rhG-CSF could increase the ex- pression of VEGF in brain tissue after HIBD, which contributes to the structural and functional restoration of brain tissue. The dose of 60 μg/kg body weight is comparatively suitable.