梓醇上调NGF、BDNF及mRNA表达伴随缺血性脑卒中大鼠神经功能恢复

目的:观察梓醇对缺血性脑卒中大鼠恢复早期神经功能恢复及缺血周围区大脑皮质神经生长因子(NGF)和脑源性神经营养因子(BDNF)表达的影响。方法:建立大鼠大脑中动脉永久性局灶性缺血模型,行为学观察各组大鼠姿势反射、横木行走和抓握力量;HE染色观察大脑皮质神经元的病理改变;免疫组织化学染色和Realtime PCR检测缺大脑皮质NGF、BDNF蛋白及其mRNA基因表达。结果:假手术组无明显神经功能障碍;与模型组比较,梓醇30、60mg/kg给药组能明显改善缺血性脑卒中大鼠姿势反射,增强横木行走的能力和抓握力量(P<0.05,P<0.01);明显增加完整神经细胞的数量(P<0.01);且梓醇30、60mg/kg给药组NGF、BDNF及mRNA的表达比模型组明显上调(P<0.05,P<0.01)。结论:梓醇可上调缺血性脑卒中大鼠大脑皮质NGF、BDNF及mRNA基因表达,促进神经元存活、修复再生,加速其神经功能恢复。

Catalpol up-regulated NGF,BDNF and mRNA gene expression and improved behavior outcome of rats with ischemic stroke

Objective:To investigate the effects of catalpol on behavior outcome of rats with ischemia stroke and the expression patterns of NGF,NGF mRNA,BDNF and BDNF mRNA in the cerebral cortex surrounding the ischemic core..Methods:Permanent cerebral ischemia was induced by middle cerebral artery occlusion in rats which were divided into 6 groups:vehicle,catalpol 15,30,60 mg/kg,dl-3n-Butyl Phthalide(NBP) 70 mg/kg and sham group.Animals received drug intragastric administration once a day 3-14 day post-ischemia.Sensorimotor function was evaluated with beam-walking and bar-grasping performance at 3,7,10 and 14 day post-ischemia,and attitudinal reflexes were assessed at the same time point.Animals were killed at 14 day post-ischemia.HE staining to observe the injury of neuron of sensorimotor region of corter.Brain sections and brain tissue homogenate were prepared for studying the expression of NGF,NGF mRNA,BDNF and BDNF mRNA in the cerebral cortex surrounding the ischemic core using immunohistochemistry and Realtime PCR methods.Results:Animals receiving catalpol at a dosage of 30、60mg/kg recovered better in attitudinal reflexes,beam-walking and bar-grasping performance than vehicles(P<0.05,P<0.01).And the gene expression of NGF,NGF mRNA,BDNF and BDNF mRNA in the model rats of the catalpol treatment group(30 and 60 mg/kg) increased significantly,higher than those in any other experiment groups(P<0.05,P<0.01).Conclusion:Catalpol can up-regulate the gene expression of NGF,NGF mRNA,BDNF and BDNF mRNA in the cerebral cortex surrounding the ischemic core,and enhance neural repairation and regeneration,which would be an underlying sub-strate for catalpol improved the functional recovery of rats with ischemic stroke.