摘要
目的观察淫羊藿苷(Ica)对血管性痴呆(VD)大鼠海马组织脑源性神经营养因子(BDNF)信号通路的影响。方法将大鼠随机分为假手术组,Ica正常对照(60 mg·kg^-1)组,模型组,Ica低、中、高剂量(15、30、60 mg·kg^-1)组(均n=8)。采用双侧颈总动脉结扎制备慢性脑低灌注诱导VD模型,仅分离颈总动脉而不结扎为假手术组,术后第9日每日灌胃给予相应剂量的Ica,连续28 d,假手术组和模型组大鼠灌胃等体积蒸馏水。Morris水迷宫实验检测大鼠空间学习记忆功能;Nissl染色观察海马神经元形态和数量;Western blot法检测BDNF信号通路关键蛋白的表达及激活。结果与假手术组大鼠相比,模型组大鼠逃避潜伏期明显延长(P<0.01),目标象限的停留时间显著减少(P<0.01),Ica中、高剂量组大鼠停留时间较模型组显著延长(P<0.05)。模型组大鼠海马CA1区神经元排列紊乱、松散,正常细胞数量较假手术组显著减少(P<0.01),Ica各剂量组神经元形态改善,正常神经元数量显著多于模型组(P<0.05)。模型组海马组织BDNF和酪氨酸激酶B(TrkB)蛋白表达量及磷酸化蛋白激酶B(p-Akt)水平均显著下降(P<0.01),细胞外调节蛋白激酶(ERK)和cAMP应答元件结合蛋白(CREB)磷酸化水平降低(P<0.05);与模型组比较,Ica中、高剂量组BDNF和TrkB蛋白表达水平、Akt磷酸化水平均显著增高(P<0.05),Ica高剂量组ERK和CREB磷酸化水平显著增高(P<0.05)。结论淫羊藿苷改善VD大鼠的学习记忆功能可能与调节海马BDNF信号通路相关。
AIM To observe the effects of icariin(Ica)on the brain-derived neurotrophic factor(BDNF)pathway in hippocampus of vascular dementia(VD)rats.METHODS Rats were divided into sham group,sham+Ica(60 mg·kg^-1)group,model group,Ica low,medium and high(15,30,60 mg·kg^-1)groups,n=8 in each group.Bilateral common carotid artery occlusion was used to prepare chronic cerebral hypoperfusion induced-VD rat model.The rats in the sham groups were only isolated the bilateral common carotid arteries but not ligated.At the 9th day after the operation,rats were treated with different doses of Ica by gavage once a day for 28 days,meanwhile sham and model groups rats were given equal volume distilled water.Morris water maze was used to test the spatial learning and memory function of rats.Nissl staining was used to observe the morphology and quantity of hippocampal neurons.Western blot was used to detect the expression and activation of key proteins of BDNF pathway in hippocampus.RESULTS Compared with the sham group,the escape latency of the model group was significantly prolonged(P<0.01),and the exploration time in the target quadrant was significantly reduced(P<0.01).The exploration time of the Ica middle and high dose groups were significantly longer than that of the model group(P<0.05).In the model group,neurons in hippocampal CA1 area were disorganized and loose,as well as the number of cells was decreased compared with the sham group(P<0.01).After different doses of Ica treatment,the morphology of neurons was improved and the number of neuron was increased(P<0.05).The protein level of BDNF and tyrosine kinase B(TrkB),and phospho protein kinase B(p-Akt)in hippocampus of the model group were significantly decreased(P<0.01),and the phosphorylation levels of extracellular regulated protein kinase(ERK)and cAMP response element-binding protein(CREB)were also significantly decreased(P<0.05).However,the protein expression of BDNF and TrkB and p-Akt in the Ica medium and high dose groups were significantly increased(P<0.05),as well as the ERK and CREB phosphorylation levels in hippocampus of the Ica high dose group were significantly increased(P<0.05).CONCLUSION The improvement of learning and memory function of VD rats after treatment with icariin may be related to the regulation of hippocampal BDNF signaling pathway.
作者
李菲
蔡锐
刘波
石京山
龚其海
LI Fei;CAI Rui;LIU Bo;SHI Jing-shan;GONG Qi-hai(Key Laboratory of Basic Pharmacology of Ministry of Education&Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi GUIZHOU 563006,China;Department of Pharmacy,People’s Hospital of Honghuagang District,Zunyi GUIZHOU 563000,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2020年第8期489-493,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
国家自然科学基金地区项目(81560594)
教育部创新团队项目(IRT_17R113)。
