甘草苷的神经保护及对胆碱酯酶的抑制作用  

Neuroprotective effects of liquiritin and its inhibitory actions on cholinesterase activity

作　　者：刘睿婷[1] 卞广兴[1] 邹莉波[2] 黄晓舞[3] 吕秋军[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]沈阳药科大学生命科学与生物制药学院,沈阳110016 [3]解放军总医院药品保障中心,北京100853

出　　处：《中国新药杂志》2008年第7期574-577,581,共5页Chinese Journal of New Drugs

摘　　要：目的：研究甘草苷（1iquiritin，LQ）的神经保护及对胆碱酯酶的抑制作用。方法：β-淀粉样蛋白（β-amyloid peptide，Aβ）25—35位氨基酸片段（Aβ25-35）作用前用不同浓度LQ预处理入神经母细胞瘤细胞（SH—SY5Y），荧光探针法检测细胞内活性氧（reactive oxygen species，ROS）水平和细胞内钙离子浓度（[Ca^2＋]i），流式细胞术检测细胞凋亡。谷氨酸作用前用LQ预处理细胞，噻唑蓝（MTT）法检测细胞存活率，检测乳酸脱氢酶（LDH）的释放情况。最后检测LQ对大鼠嗜铬细胞瘤细胞（PC12）胆碱酯酶的抑制作用。结果：LQ（0．1，1，10μmol·L^-1）能够抑制Aβ25-35引起的细胞内ROS水平和[Ca^2＋]i升高，减少细胞凋亡；同浓度的LQ能够减少谷氨酸引起的LDH释放，提高细胞存活率；LQ（1，5，25μmol·L^-1）能够特异性抑制乙酰胆碱酯酶活性，而对丁酰胆碱酯酶活性无明显抑制作用。结论：LQ能够抑制Aβ25-35及谷氨酸的神经毒性，且能够特异性抑制乙酰胆碱酯酶活力，可能对阿尔茨海默病的预防或治疗具有一定研究价值。Objective： To estimate neuroprotective ettects of liquiritin（LQ） and its inhibitor actions on cholinesterase activity. Methods： SH-SY5Y cells were pretreated with indicated concentrations of LQ prior to β- amyloid peptide fragment 25 - 35 （Aβ25-35） exposure. Then intracellular reactive oxygen species （ROS） level and intracellular calcium concentration （ [ Ca^2＋ ]i） were detected using fluorescence probe, and apoptosis rate of the cells was detected by flow cytometry. After SH-SY5Y cells were preincubated with LQ prior to exposure to glutamate, the cell viability was determined by MTT assay, and LDH release was also measured. The inhibitory effects of LQ on cholinesterase were examined in PC12 cells. Results： Pretreatment with LQ （0.1, 1, 10/μmol·L^-1） markedly attenuated Aβ25-35,-increased ROS level and [ Ca^2＋]i, and inhibited Aβ25-35-induced apoptosis. LQ decreased glutamate-induced LDH release, and significantly increased cell survival. In addition, LQ （1,5,25 /μmol· L^- 1 ） inhibited the acetylcholinesterase （AchE） activity but not the butyrylcholinesterase （BuChE） activity. Conclusion： LQ exhibits protective effects on Aβ25-35 and glutamate-induced toxicity, and it has specific inhibitory actions on AchE activity. It suggests that LQ may be a potential multipotent agent for treating or preventing Alzheimer＇s disease （AD）

关 键 词：甘草苷 Β-淀粉样蛋白 谷氨酸 胆碱酯酶 阿尔茨海默病 多靶向 

分 类 号：R965.1[医药卫生—药理学] R971.9[医药卫生—药学]