生慧汤对APP/PS1雄性AD小鼠海马内APP代谢产物的昼夜变化影响  

Effect of Shenghui Decoction on Diurnal Changes of APP Metabolites in Hippocampus of APP/PS1 Male Mice

作　　者：文纯 游秋云 王平 丁莉 Wen Chun;You Qiu Yun;Wang Ping;Ding Li(College of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China;Institute of Gerontology of Hubei University of Traditional Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]湖北中医药大学老年医学研究所,武汉430065

出　　处：《世界科学技术-中医药现代化》2022年第8期3212-3218,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会青年科学基金项目(81703972):基于生物钟基因对神经炎症的调控研究补肾安神益智法对阿尔茨海默病的干预作用;负责人:丁莉

摘　　要：目的研究生慧汤对APP/PS1(β-amyloid precursor protein/presenilin 1246E)小鼠海马内β淀粉样前体蛋白(Amyloid precursor protein,APP)代谢产物昼夜表达的影响。方法将56只雄性APP/PS1双转基因痴呆模型小鼠随机分为4组,分别为:痴呆模型组、褪黑素治疗组(0.78 mg·kg^(-1)·d^(-1))、生慧汤高剂量组(27.0 g·kg^(-1)·d^(-1))、生慧汤低剂量组(13.5 g·kg^(-1)·d^(-1)),每组14只;对照组为14只雄性C57BL/6J小鼠,连续给药30天。采用Morris水迷宫检测小鼠学习记忆能力,采用酶联免疫吸附检测(ELISA)检测不同时间段取出的海马组织sAPPα含量。对海马β淀粉样蛋白_(1-40)、β淀粉样蛋白_(1-42)表达进行免疫印迹分析。免疫组化(IHC)检测海马CA1区Aβ_(1-40)蛋白的表达。结果Morris水迷宫结果表明,与对照组相比,模型组上平台潜伏期明显延长、穿越平台次数明显减少(P<0.01);与模型组相比,生慧汤不同剂量组上平台潜伏期明显缩短(P<0.01、P<0.05),穿越平台次数明显增加(P<0.05)。ELISA结果表明,与对照组相比,模型组的sAPPα总量、各时间段(12:00、24:00)sAPPα含量明显减少(P<0.01);与模型组相比,生慧汤不同剂量组sAPPα总量明显增多(P<0.01、P<0.05),生慧汤高剂量组仅能增加12:00 sAPPα含量(P<0.01),生慧汤低剂量组仅能增加24:00 sAPPα含量(P<0.05)。对照组sAPPα含量具有明显昼夜差异(P<0.01)。模型组sAPPα含量的昼夜差异性消失(P>0.05)。生慧汤高剂量组sAPPα含量具有昼夜差异(P<0.01),生慧汤低剂量组sAPPα含量不具有昼夜差异(P>0.05)。Western blot结果显示,与对照组相比,模型组Aβ_(1-40)、Aβ_(1-42)蛋白表达明显增加(P<0.01);与模型组相比,生慧汤高剂量组Aβ_(1-40)、Aβ_(1-42)蛋白表达减少(P<0.05、P<0.01);生慧汤低剂量组仅能减少Aβ_(1-40)蛋白的表达(P<0.05),对Aβ_(1-42)蛋白表达无影响(P>0.05)。免疫组化结果表明,与对照组相比,模型组Aβ_(1-40)表达明显增加(P<0.01);与�Objective To study the effect of Shenghui decoction on the diurnal expression of amyloid precursor protein(APP)metabolites in the hippocampus of APP/PS1 mice.Methods Fifty-six male APP/PS1 double transgenic mice with dementia were randomly divided into 4 groups,dementia model group,melatonin treatment group(0.78 mg·kg^(-1)·d^(-1)),high dose group of Shenghui decoction(27.0 g·kg^(-1)·d^(-1))and low dose group of Shenghui decoction(13.5 g·kg^(-1)·d^(-1)).14male C57BL/6J mice in control group,30 days of continuous administration.The learning and memory ability of mice was tested by Morris water maze.The level of sAPPαin different time was detected by enzyme-linked immunosorbent assay(ELISA).The expression ofβamyloid protein_(1-40)andβamyloid protein_(1-42)in hippocampus were analyzed by western blotting.The expression ofβamyloid protein_(1-40)in hippocampus CA1 region was detected by immunohistochemistry(IHC).Results The results of Morris water maze showed that compared with the control group,the latency of the platform in the model group was significantly prolonged and the number of crossing the platform was significantly reduced(P<0.01).Compared with the model group,the incubation period of the platform was significantly shortened(P<0.01,P<0.05),and the number of crossing the platform was significantly increased(P<0.05)in different dose groups of Shenghui decoction.ELISA results showed that compared with the control group,the total amount of sAPPαand the sAPPαcontent at each time period(12:00 and 24:00)were significantly reduced in the model group(P<0.01).Compared with the model group,the total amount of sAPPαwas significantly increased in the Shenghui decoction group(P<0.01and P<0.05),and only the sAPPαcontent at 12:00 was increased in the high dose group of Shenghui decoction(P<0.01),the sAPPαcontent at 24:00 was increased in the low dose group of Shenghui decoction(P<0.05).The sAPPαcontent had significant diurnal differences in the control group(P<0.01).However,it was disappeared in the model gr

关 键 词：阿尔茨海默症 生慧汤 雄性APP/PS1双转基因痴呆模型小鼠 淀粉样前体蛋白代谢 昼夜节律 

分 类 号：R285.5[医药卫生—中药学]