基于明确靶标及分子对接验证技术探究五味子醇甲对阿尔茨海默病的作用机制  

Action Mechanism of Schisandrin A on AD Based on Clear Targetand Molecular Docking Verification Technology

作　　者：狄舒男 郭译文 桑希生[2] 周妍妍[2] 于淼[2] 徐世杰[1] DI Shunan;GUO Yiwen;SANG Xisheng;ZHOU Yanyan;YU Miao;XU Shijie(Institute of Basic Theory of Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700 [2]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《中医药学报》2023年第5期21-26,共6页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金青年基金项目(81803984);黑龙江省教育科学规划领导小组2021年度“十四五”规划重点课题(GJB1421307)。

摘　　要：目的:明确五味子醇甲对阿尔茨海默病的作用机制。方法:选取24只大鼠按体质量随机分为空白组、模型组和给药组,每组8只。采用对大鼠海马CA1区注射Aβ1-40的方法制备阿尔茨海默病大鼠模型,造模1 d后灌胃给予30 mg/kg的五味子醇甲溶液,造模7 d后,进行Morris水迷宫行为学测试。在此基础上,对与阿尔茨海默病明确相关的β-分泌酶、雌激素受体β(ERβ)、谷氨酸受体1(NMDAR1)等蛋白进行验证,以蛋白表达量及药物成分与靶标作用的分子对接能进行评价,并通过分子对接技术计算五味子醇甲与各蛋白的对接能,达到理论验证的目的。结果:与空白组比较,模型组大鼠海马组织匀浆中β-分泌酶的活性含量明显增加(P<0.01),大鼠海马组织中ERβ表达显著降低(P<0.01),P-P38/P38表达明显升高(P<0.01),BACE1表达显著升高(P<0.01),NMDAR1表达明显降低(P<0.01);与模型组比较,给药组大鼠海马组织匀浆中β-分泌酶的活性含量明显减少(P<0.01),给药组大鼠海马组织中ERβ表达显著升高(P<0.01),P-P38/P38表达显著降低(P<0.01),BACE1表达显著降低(P<0.01),NMDAR1表达显著升高(P<0.01)。分子对接结果显示五味子醇甲与各靶蛋白对接的分子对接能稳定,从理论验证结果的可靠性。结论:基于已知靶点的五味子醇甲成分验证结果可知,五味子醇甲治疗阿尔茨海默病具有多成分、多靶点及多途径的作用特点,其作用机制可能与已知的阿尔茨海默病代谢通路直接相关,且通过对Beta-Secretase 1、ERβ、P-P38/P38、BACE1和NMDAR1蛋白的靶向调控实现。Objective:To clarify the mechanism of Schisandrin A on Alzheimer s disease(AD).Methods:24 rats were randomly divided into the blank group,the model group and the medication group.The model of AD was established by the injection of Aβ1-40 into the CA1 area of hippocampus in the rats.After 1 day of modeling,Schisandrin A(30 mg/kg)solution was given by gavage.After 7 days of modeling,Morris water maze behavioral test was performed.The proteins ofβ-Secretase 1,estrogen receptorβ(ERβ),N-methyl-D-aspartate receptor 1(NMDAR1)were verified.The protein expression and the molecular docking energy of the drug components and the target function were evaluated.The docking energy of Schisandrin A and each protein was calculated by molecular docking technology to achieve the purpose of theoretical verification.Results:Compared with those in the control group,the activity ofβ-secretory enzyme was significantly increased(P<0.01),the expression of ERβwas significantly decreased(P<0.01),the expression of P-P38/P38 was significantly increased(P<0.01),the expression of BACE1 was significantly increased(P<0.01),and the expression of NMDAR1 was significantly decreased in the model group(P<0.01).Compared with those in the model group,the activity ofβ-Secretase 1 was significantly decreased(P<0.01),the expression of ERβwas significantly increased(P<0.01),the expression of P-P38/P38 was significantly decreased(P<0.01),the expression of BACE1 was significantly decreased(P<0.01),and the expression of NMDAR1 was significantly increased in the medication group(P<0.01).The molecular docking results showed that the molecular docking energy of Schisandrin A and target proteins were stable,and the reliability of the results was verified theoretically.Conclusion:Based on the verification results of Schisandrin A with known targets,Schisandrin A has the characteristics of multiple components,multiple targets and multiple pathways in treatment of AD.Its action mechanism may first be directly related to the known metabolic pathway of AD,and t

关 键 词：五味子醇甲 阿尔茨海默病 Β-分泌酶 雌激素受体Β 谷氨酸受体1 

分 类 号：R285.5[医药卫生—中药学]