基于尿代谢组学的恒清Ⅱ号方治疗阿尔茨海默病作用及其机制的实验研究  

Effect of HengqingⅡDecoction on Alzheimer′s Disease and Its Mechanism Based on Urinary Metabonomics

作　　者：孟胜喜[1] 霍清萍[1] 王兵[1] 付剑亮[1] 彭文波[1] 王宇新[1] 梁芳[1] 汪天湛[1] 张洪艳[1] 余忠海 彭学丰 李学敏[1] 曹健美 李文涛[3] MENG Shengxi;HUO Qingping;WANG Bing;FU Jianliang;PENG Wenbo;WANG Yuxin;LIANG Fang;WANG Tianzhan;ZHANG Hongyan;YU Zhonghai;PENG Xuefeng;LI Xuemin;CAO Jianmei;LI Wentao(Shanghai Sixth People′s Hospital,Affiliated to Shanghai Jiao Tong University,Shanghai 200233,China)

机构地区：[1]上海交通大学附属第六人民医院,上海200233 [2]上海中医药大学研究生院 [3]上海市中医医院

出　　处：《中西医结合心脑血管病杂志》2020年第17期2794-2800,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：上海市科委2019年度“科技创新行动计划”临床医学领域科技支撑项目(No.19401970600);上海市科委项目(No.19401932500);上海市进一步加快中医药事业发展三年行动计划(2018年—2020年)中医药重大临床研究[No.ZY(2018-2020)-CCCX-4010];上海交通大学医学院中西医结合创新基金(No.18zxy002);上海交通大学医学院2019年度教师培训发展项目(No.JFXM201909)。

摘　　要：目的基于尿代谢组学探讨恒清Ⅱ号方治疗阿尔茨海默病(AD)小鼠的作用及其机制。方法将APPswe/PS1dE9双转基因AD模型小鼠随机分为模型组(model组)、恒清Ⅱ号方低剂量组(HQ-L组)、恒清Ⅱ号方中剂量组(HQ-M组)、恒清Ⅱ号方高剂量组(HQ-H组)、安理申组(Aricept组),每组10只。同月龄C57BL/6J小鼠10只作为正常组(normal组)。采用水迷宫测试各组小鼠认知功能,以代谢组学技术筛选AD小鼠尿液生物标记物,并分析其对应的代谢通路。结果在改善小鼠认知功能方面,与model组比较,HQ-M组、HQ-H组、Aricept组小鼠逃避潜伏期(EL)明显缩短(P<0.01),穿越平台次数(NCP)明显增加(P<0.01);与HQ-L组比较,HQ-M组、HQ-H组、Aricept组小鼠EL明显缩短,NCP明显增加,差异均有统计学意义(P<0.05或P<0.01);与HQ-M组比较,HQ-H组小鼠EL明显缩短(P<0.05),NCP明显增加(P<0.05);与Aricept组比较,HQ-H组小鼠EL明显缩短(P<0.05),NCP明显增加(P<0.05)。恒清Ⅱ号方低、中、高剂量之间的作用比较:HQ-H组>HQ-M组>HQ-L组,恒清Ⅱ号方的量效关系呈正相关;高剂量恒清Ⅱ号方与安理申之间的作用比较,HQ-H组>Aricept组,即高剂量恒清Ⅱ号方的作用要优于安理申。与normal组比较,model组尿液中α-生育三烯酚、鞘氨醇激酶、多巴胺含量均降低,胆固醇含量均升高,差异均有统计学意义(P<0.01);与模型组比较,HQ-M组、HQ-H组、Aricept组α-生育三烯酚、鞘氨醇激酶、多巴胺含量均升高,胆固醇含量均降低,差异均有统计学意义(P<0.01);与HQ-L组比较,HQ-M组、HQ-H组、Aricept组α-生育三烯酚、鞘氨醇激酶、多巴胺含量均升高,胆固醇含量均降低,差异均有统计学意义(P<0.01);与HQ-M组比较,HQ-H组、Aricept组α-生育三烯酚、鞘氨醇激酶、多巴胺含量均升高,胆固醇含量均降低,差异均有统计学意义(P<0.01);与Aricept组比较,HQ-H组α-生育三烯酚、鞘氨醇激酶、多巴胺含量均升高,胆固醇含量均降�Objective To study the effect of HengqingⅡdecoction(HQ)on Alzheimer′s disease(AD)mice and its mechanism based on urinary metabonomics.Methods APPswe/PS1dE9 double transgenic AD model mice were randomly divided into model group,HQ low dose(HQ-L)group,HQ medium dose(HQ-M),HQ high dose(HQ-H)group,Aricept group,10 mice in each group.Ten C57BL/6J mice of the same age were selected as normal group.Water maze was used to test the cognitive function of each group of mice.Urine biomarkers of AD mice were screened by metabolomics and their corresponding metabolic pathways were analyzed.Results In terms of improving the cognitive function of mice,compared with model group,escape latencies(EL)of mice in HQ-M group,HQ-H group,and Aricept group were significantly shortened and number of crossing platforms(NCP)in HQ-M group,HQ-H group,and Aricept group were significantly increased(P<0.01).Compared with HQ-L group,EL of mice in HQ-M group,HQ-H group,and Aricept group were significantly shortened,and NCP in HQ-M group,HQ-H group,and Aricept group were significantly increased(P<0.05 or P<0.01).Compared with HQ-M group,EL of HQ-H group was significantly shortened and NCP was significantly increased(P<0.05).Compared with the Aricept group,EL of HQ-H group was significantly shortened and NCP was significantly increased(P<0.05).HQ′s dose-effect relationship was positive.Comparison of effects between low,medium and high doses:HQ-H group>HQ-M group>HQ-L group,the dose-effect relationship of HQ was positively correlated.Comparison of effects between HQ-H and Aricept:HQ-H group>Aricept group.The effect of high dose HQ was superior to that of Aricept.Compared with the normal group,the levels ofα-tocotrienol,sphingsine,and dopamine in model group were decreased(P<0.01),and the level of cholesterol in model group was increased(P<0.01).Compared with model group,the levels of alpha-tocotrienol,sphingsine,and dopamine in HQ-M group,HQ-H group,and Aricept group were increased(P<0.01),and the levels of cholesterol in HQ-M group,HQ-H group,

关 键 词：阿尔茨海默病 恒清Ⅱ号方 尿代谢组学 生物标记物 代谢通路 实验研究 

分 类 号：R747.89[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]