天智颗粒对VD大鼠海马SYN、PSD95表达及突触可塑性的影响  

Effects of Tianzhi Granule on SYN,PSD95 Expression and Synaptic Plasticity in Hippocampus of VD Model Rats

作　　者：张鹏飞[1] 姚晰晨 刘晨 徐冰倩 郭水柱 高爱社[1] 孙宁[1] ZHANG Pengfei;YAO Xichen;LIU Chen;XU Bingqian;GUO Shuizhu;GAO Aishe;SUN Ning(Henan University of Chinese Medicine,Zhengzhou Henan China 450046;Henan Province Technological Innovation Center for Solid Preparation of Traditional Chinese Medicine,Zhongjing Wanxi Pharmaceutical Co.,Ltd,Nanyang Henan China 474500)

机构地区：[1]河南中医药大学,河南郑州450046 [2]仲景宛西制药股份有限公司河南省中药固体制剂技术创新中心,河南南阳474500

出　　处：《中医学报》2023年第8期1717-1724,共8页Acta Chinese Medicine

基　　金：河南省卫生健康委专项课题项目(20-21ZY2145,20-21ZY2158);河南中医药大学研究生科研创新基金项目。

摘　　要：目的:观察天智颗粒对血管性痴呆(vascular dementia,VD)模型大鼠认知功能障碍及神经元突触可塑性的影响。方法:采用双侧颈总动脉永久性结扎法制备VD模型,将造模成功大鼠按体质量分为模型组、多奈哌齐组(0.45 mg·kg^(-1))及天智颗粒低(0.66 g·kg^(-1))、中(1.32 g·kg^(-1))、高(2.65 g·kg^(-1))剂量组,另设假手术组,每组12只。灌胃给药8周后,Morris水迷宫检测大鼠的学习记忆能力;HE染色观察海马CA1区神经元损伤情况;透射电子显微镜观察海马CA1神经元突触结构改变情况;Western Blot检测海马组织突触素(synaptophysin,SYN)、突触后致密蛋白95(postsynaptic density protein 95,PSD95)的蛋白表达水平。结果:与模型组比较,天智颗粒组大鼠逃避潜伏期明显缩短(P<0.05),平台所在象限时间占比和平台穿越次数明显增多(P<0.05),海马神经元突触间隙宽度显著减小(P<0.01),海马组织SYN、PSD95蛋白表达水平显著升高(P<0.05);HE染色及透射电镜观察显示,天智颗粒可明显改善VD大鼠海马CA1区神经元排列紊乱和突触超微结构损伤。结论:天智颗粒能明显改善VD模型大鼠认知障碍,机制可能与其修复神经元及突触超微结构损伤、提高SYN、PSD95蛋白表达水平从而改善突触可塑性有关。Objective:To observe the effect of Tianzhi Granule on cognitive dysfunction and synaptic plasticity of neurons in rats with vascular dementia(VD)model.Methods:VD model was prepared by permanent ligation of bilateral common carotid artery,and rats with successful modeling were divided into model group,donepezil group(0.45 mg·kg^(-1)),low(0.66 g·kg^(-1)),medium(1.32 g·kg^(-1)),high(2.65 g·kg^(-1))dose groups according to body weight,and a sham surgery group,each group of 12 animals.Eight weeks after gavage,the Morris water maze detected the learning and memory ability of rats;neuronal damage in the CA1 region of the hippocampus was observed with HE staining.The synaptic structure of CA1 neurons in the hippocampus was observed with Transmission electron microscopy.Western Blot measures the expression levels of synaptophysin(SYN)and postsynaptic density protein 95(PSD95)in hippocampal tissues.Results:Compared with the model group,the evasion latency of rats in the Tianzhi Granule group was significantly shortened(P<0.05),the proportion of quadrant time and the number of platform crossings increased significantly(P<0.05),the synaptic gap width of hippocampal neurons was significantly reduced(P<0.01);the hippocampal tissue SYN and the expression level of PSD95 protein was significantly increased(P<0.05).With HE staining and transmission electron microscopy,it is suggested that Tianzhi Granule could significantly improve neuronal arrangement disorder and synaptic ultrastructural damage in the CA1 region of the hippocampus in VD rats.Conclusion:Tianzhi Granule can significantly improve cognitive impairment in VD model rats,and the mechanism may be related to its repair of neuronal and synaptic ultrastructural damage,increase the expression level of SYN and PSD95 proteins,and thus improve synaptic plasticity.

关 键 词：血管性痴呆 天智颗粒 突触素 突触后致密蛋白95 突触可塑性 大鼠 

分 类 号：R285.5[医药卫生—中药学]