松果菊苷对血管性痴呆大鼠学习记忆及海马组织BDNF、TrkB表达的影响  

Effect of Echinacoside on Learning-Memory Function and Expression of BDNF and TrkB in Hippocampal Tissue of Vascular Dementia Rats

作　　者：杨倩[1,2] 孙蓉[2] 

机构地区：[1]山东中医药大学,山东济南250355 [2]山东省中医药研究院,山东济南250014

出　　处：《中药新药与临床药理》2017年第3期304-309,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家重大新药创制重大专项课题(2009ZX09502-015);山东省自主创新和成果转化项目(2014ZZCX02104);泰山学者工程专项经费资助(ts201511107)

摘　　要：目的通过建立血管性痴呆(VD)大鼠模型,观察松果菊苷(ECH)对VD大鼠学习记忆及海马组织脑源性神经营养因子(BDNF)、酪氨酸激酶B(TrkB)表达的影响。方法取SD大鼠随机分为假手术组、模型组和ECH组(30 mg·kg^(-1)),每组30只。采用永久性结扎双侧颈总动脉建立大鼠VD模型,ECH组给予ECH治疗4周,采用Morris水迷宫检测学习记忆能力,处死大鼠取脑,分离皮层与海马组织,HE染色观察脑组织神经元损伤。RT-PCR法测定海马组织BDNF、TrkB mRNA表达,Western blot法检测BDNF、TrkB、AKT蛋白表达水平,免疫组化法测定N-甲基-D-天冬氨酸受体(NMDAR)蛋白的表达。结果与假手术组比较,模型组大鼠逃避潜伏期延长,穿越平台次数降低(P<0.05),脑组织皮质及海马组织神经元损伤明显,海马组织BDNF、TrkB mRNA表达及BDNF、TrkB、AKT、NMDAR蛋白表达低于假手术组(P<0.05);与模型组比较,ECH组大鼠逃避潜伏期缩短,穿越平台次数增加(P<0.05),脑组织皮质及海马组织神经元损伤明显改善,海马组织BDNF、TrkB的mRNA表达及BDNF、TrkB、AKT、NMDAR蛋白表达明显高于模型组(P<0.05)。结论松果菊苷可能通过上调VD大鼠海马区BDNF、TrkB、AKT、NMDAR表达,减轻VD大鼠神经元缺血损伤,改善学习记忆能力。Objective To observe the effect of echinacoside （ECH） on learning-memory function and the expression, of brain-derived neurotropic factor （BDNF） and tyrosine kinase B（TrkB） in hippocampal tissue of vascular dementia （VD） rats. Methods Ninety six-month-old male SD rats were randomly divided into sham operation group,model group and ECH group（30 mg·kg^-1）, 30 rats in each group. Rat model of vascular dementia （VD） was established by permanent occlusion of bilateral carotid artery. Rats in ECH group were administered with ECH for 4 weeks. Learning and memory abilities were detected by using the Morris water maze. The cortex and hippocampus tissue were separated after rats were sacrificed. Cerebral neuronal damage was observed by HE staining. Expression of TrkB and BDNF mRNA in the hippocampus was detected by RT-PCR, protein expression of BDNF, TrkB, and AKT was detected by Western blot method, and NMDAR protein expression was examined by immunohistochemical method. Results Escape latency of rats in the model group was prolonged and the number of crossing platform were decreased, neuronal damage in the cortex and hippocampus was obvious, BDNF and TrkB mRNA expression levels as well as BDNF, TrkB, AKT and NMDAR protein expression in the hippocampus tissue were decreased as compared with those in the sham operation group （P 〈 0.05）. Compared with the model group, the escape latency in ECH group was significantly shortened and the number of crossing platform was increased, neuronal damage in the cortex and hippocampus tissues was significantly improved, BDNF and TrkB mRNA expression levels as well as BDNF, TrkB, AKT and NMDAR protein expression in the hippocampus tissue were decreased （P 〈 0.05）. Conclusion Echinacoside can relieve the neuronal damage and improve learning-memory function in VD rats probably by up-regulating the expression of BDNF,TrkB, AKT and NMDAR in rat hippocampus.

关 键 词：松果菊苷 血管性痴呆 脑源性神经营养因子 酪氨酸激酶B 

分 类 号：R285.5[医药卫生—中药学]