琥珀调控颈总动脉结扎脑缺血大鼠海马区神经元凋亡改善大鼠学习与记忆能力的效用部位与作用机制研究  

Researches on Effective Fraction and Mechanism of Amber Improving Learning and Memory on Rats with Carotid Artery Ligation via Regulation of Neuronal Apoptosis in Hippocampus

作　　者：魏翀琦 曹程 刘梦秋[1] 曲苏晨 楼倩颖 段金廒[1] 尚尔鑫[1] 朱悦[1] Wei Chongqi;Cao Cheng;Liu Mengqiu;Qu Suchen;Lou Qianying;Duan Jin'ao;Shang Erxin;Zhu Yue(School of Pharmacy,Nanjing University of Chinese Medicine,Jiangsu Key Laboratory for Modern Research of Traditional Chinese Medicine Formulae,Jiangsu Key Laboratory for High Technology Research of TCM Formulae,Nation and Local Union Project Research Center of Chinese Medicinal Resources Industrialization and Innovative Drug from TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院/江苏省方剂研究重点实验室/江苏省方剂高技术研究重点实验室/中药资源产业化与方剂创新药物国家地方联合工程研究中心/江苏省中药资源产业化过程协同创新中心,南京210023

出　　处：《世界科学技术-中医药现代化》2022年第1期88-97,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：南京中医药大学江苏省中药资源产业化过程协同创新中心重点项目(ZDXM-2020-15):中药琥珀的功效物质基础与作用机制研究,负责人:尚尔鑫;江苏省教育厅江苏省研究生科研与实践创新计划(SJCX20_0567):麋鹿角“通利血脉”改善血管性痴呆的功效物质基础研究,负责人:魏翀琦;江苏省教育厅江苏省研究生科研与实践创新计划(KYCX20_1580):基于神经营养因子调控和神经生长的麋鹿角抗抑郁作用机制研究,负责人:刘梦秋。

摘　　要：目的琥珀调控海马区神经元凋亡改善颈总动脉结扎脑缺血大鼠学习与记忆能力的效用部位与作用机制研究。方法建立大鼠颈总动脉结扎脑缺血动物模型,给以模型动物琥珀系列溶剂提取部位,通过水迷宫实验评价琥珀提取部位对模型动物学习与记忆能力的影响。采用TUNEL染色法与蛋白印迹法分别评价琥珀提取部位对模型动物海马区细胞凋亡以及Caspase 3、Caspase 9、Bcl-2等凋亡相关蛋白表达的影响。采用小鼠海马永生化细胞系评价琥珀提取部位对抗糖氧剥夺神经元损伤的作用。结果琥珀乙酸乙酯提取部位显著改善模型大鼠学习与记忆能力,抑制海马区细胞凋亡。该提取部位还可显著提高糖氧剥夺状态下HT22细胞的存活率,并下调细胞中Caspase 3、Caspase 9和Bcl-2等凋亡通路蛋白表达水平。结论乙酸乙酯提取部位是琥珀药材改善颈总动脉结扎脑缺血大鼠的学习与记忆能力效用部位,抑制海马区细胞凋亡是其作用机制。Objective To explore the anti-vascular dementia(VD) mechanism of Amber via regulation of neuronal apoptosis in hippocampus of rats with carotid artery ligation. Methods A vascular dementia rat model induced by ligation of carotid artery was established and different amber extracts were given to the model animals. The anti-vascular dementia effects of amber extracts were evaluated on carotid artery ligation rats by Morris water maze. In addition, the effect of amber extract on apoptosis was evaluated by TUNEL staining and the expressions of Caspase 3, Caspase 9, Bcl-2 and other apoptosis related proteins and was evaluated by Western blotting. Furthermore, mouse hippocampal immortalized cell lines(HT22) were established to evaluate the protective effect of the amber extracts on oxygen glucose deprivation(OGD) damages.Results Ethyl acetate extract of amber could improve the learning and memory of carotid artery ligation rats and increase the cell viability of HT22 cells. Ethyl acetate extract of amber also decreased the expressions of Caspase 3, Caspase 9, Bcl-2 and other apoptosis signal pathway proteins both on hippocampus tissues and cell lines. Conclusion Regulation of neuronal apoptosis in hippocampus might contribute to the anti-vascular dementia effect of amber and the ethyl acetate extracts might be the effective fraction.

关 键 词：琥珀 神经元凋亡 血管性痴呆 有效部位 

分 类 号：R285.5[医药卫生—中药学]