丁基苯酞对大鼠局灶缺血脑组织VEGF及bFGF表达的影响

目的研究丁基苯酞(NBP)对大鼠缺血脑组织中血管内皮生长因子(VEGF)和碱性成纤维生长因子(bFGF)表达的影响。方法健康雄性SD大鼠,用大鼠大脑中动脉线栓法(MCAO)建立永久缺血模型。实验分为假手术组、模型对照组和NBP组,每组各20只大鼠。NBP组术后予以NBP灌胃,每天2次,每次25mg/kg;假手术组、模型对照组每天灌胃相应剂量食用植物油。局灶性缺血72h后行神经功能评分(Longa评分),然后断头取脑。TTC染色观察脑梗死体积,免疫组织化学(SP)方法观察梗死周围区、海马区和梗死核心区脑组织VEGF和bFGF蛋白的表达,原位杂交方法(POD法)检测VEGF mRNA和bFGF mRNA的表达。结果NBP组神经功能缺损评分低于模型对照组(P<0.05),NBP组在梗死周围区和海马区VEGF和bFGF蛋白,VEGF mRNA和bFGFmRNA表达均高于模型对照组和假手术组(P<0.05),在梗死核心区差异均无统计学意义(P>0.05)。结论NBP明显改善缺血后大鼠的神经功能,上调大鼠梗死周围区和海马区脑组织VEGF、bFGF蛋白和mRNA的表达,可能通过此机制治疗保护缺血脑组织。

Effects of dl-3-n-butylphthalide on Expression of VEGF and bFGF in Rat Brain with Permanent Focal Cerebral Ischemia

Objective To study the effects of dl-3n-butylphthalide(NBP)on the protein and mRNA expression of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in rats brain with permanent middle cerebral artery occlusion(MCAO).Methods The model of permanent MCAO was established by using the suture method of Longa,with which the nylon suture was used to make rat middle cerebral artery(MCA)blocked.Sham-operated rats(n=20)were prepared in similar fashion,but without doing the closed occlusion of the MCA.Operated rats were randomizely divided into model control and NBP groups(n=20 for each).By intragastric administration,sham-operated and model control group rats were given vegetable oil 2 mL twice daily for 3 days,and also NBP group rats were given NBP 25 mg/kg twice daily for 3 days.The infarct volume and neurological deficit scores were determined by tetrazolium chloride(TTC)staining and Longa's score separately.The protein and mRNA of VEGF and bFGF were detected by immunohistochemistry and in situ hybridization.Results NBP markedly inhibited the neurological deficit and reduced the infarct volumes as compared to model control group(P<0.05).NBP significantly upregulated VEGF and bFGF expression in both protein and mRNA levels in the peripheral infarct and hippocampus regions in contrast with sham-operated and model control groups(P<0.05).In the infarct core,the protein and mRNA levels of VEGF and bFGF did not show significantly any difference(P>0.05).Conclusion NBP can significantly reduce neurological deficit and infarction volume,and therefore may have protective effect for cerebral ischemia through upregulating the expression of VEGF and bFGF.