温肺降浊方调节Nogo-A、NgR表达对VaD大鼠神经元突触重塑的影响

Effect of Wenfei Jiangzhuo prescription on neuronal synaptic plasticity in rats with vascular dementia by regulating the expression of Nogo-A and NgR

目的:观察温肺降浊方对血管性痴呆(VaD)大鼠Nogo-A和NgR mRNA及其蛋白表达的影响。方法:将30只大鼠随机分为假手术组、模型组、中药组,每组各10只。采用双侧颈总动脉永久性结扎方法制作VaD大鼠模型,造模成功后中药组予温肺降浊方灌胃,假手术组、模型组予以等量0.9%氯化钠注射液灌胃,疗程均为4周。采用Morris水迷宫行为学测试大鼠学习记忆能力;RT-PCR、Western blot检测各组大鼠Nogo-A和NgR mRNA及其蛋白表达水平,透射电镜观察神经元突触结构变化。结果:与假手术组比较,模型组大鼠逃避潜伏期延长、穿越平台次数减少(P<0.01或P<0.05);海马中Nogo-A和NgR蛋白及mRNA表达增多(P<0.01)。与模型组比较,中药组逃避潜伏期缩短、穿越平台次数增加(P<0.05);海马中Nogo-A和NgR mRNA及其蛋白减少(P<0.05)。海马神经元突触及细胞器完整、突触间隙及小泡正常。结论:温肺降浊方可改善VaD大鼠学习记忆能力,其机制可能与降低Nogo-A和NgR mRNA及蛋白表达含量,促进神经突触再生,改善海马突触可塑性有关。

Objective:To investigate the effect of Wenfei Jiangzhuo prescription on the mRNA and protein expre ssion levels of Nogo-A and NgR in rats with vascular dementia(VaD).Methods:A total of 30 rats were randomly divided into sham-operation group,model group,and traditional Chinese medicine(TCM)group,with 10 rats in each group.Permanent occlusion of both common carotid arteries was performed to establish a rat model of VaD,and after suc-cessful modeling,the rats in the TCM group were given Wenfei Jiangzhuo prescription by gavage,while those in the sham-operation group and the model group were given an equal volume of 0.9%sodium chloride injection by gavage,with a course of treatment of 4 weeks for all groups.The Morris water maze was used to assess learning and memory abilities;RT-PCR and Western blot were used to measure the mRNA and protein expression levels of Nogo-A and NgR;a transmission electron microscope was used to observe the change in neuronal synaptic structure.Results:Compared with the sham-oper-ation group,the model group had a significant increase in escape latency and a significant reduction in the number of plat-form crossings(P<0.01 or P<0.05),as well as significant increases in the protein and mRNA expression levels of Nogo-A and NgR in the hippocampus(P<0.01).Compared with the model group,the TCM group had a significant reduction in escape latency and a significant increase in the number of platform crossings(P<0.05),as well as significant reductions in the protein and mRNA expression levels of Nogo-A and NgR in the hippocampus(P<0.01).Hippocampal neurons had complete synapses and organelles,with normal synaptic cleft and vesicle.Conclusion:Wenfei Jiangzhuo prescription can improve the learning and memory abilities of VaD rats,possibly by reducing the mRNA and protein expression levels of No-go-A and NgR,promoting neuronal synapse regeneration,and improving hippocampal synaptic plasticity.