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灵芝制剂对APP/PS1双转基因阿尔茨海默病模型小鼠的行为学、生物化学和自身免疫指标的影响
Effect of Ganoderma Lucidum Preparation on the Behavior,Biochemistry, and Autoimmune Parameters of Mouse Models of APP/PS1 Double Transgenic Alzheimer's Disease

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秦川 1   吴善球 2   陈保生 3 *   吴小闲 1   屈焜耀 2   刘军民 4   张桂芳 4   徐艳峰 1   舒顺利 2   孙丽华 1   李彦红 1   朱华 1   黃澜 1   马春梅 1   徐玉环 1   韩云林 1   卢耀增 1 *  
文摘 目的评估灵芝制剂对APP/PS1双转基因阿尔茨海默病(AD)小鼠行为学、生物化学和自身免疫指标的影响。方法将44只4月龄APP/PS-1双转基因AD小鼠随机分为AD模型组、安理申组、灵芝中剂量组和灵芝高剂量组4组,每组11只,以10只4月龄C57BL/6小鼠为对照组。水迷宫实验观测小鼠的行为学变化情况,Western blot法检测脑组织蛋白表达水平,间接免疫荧光法检测自身免疫指标。结果定位航行实验结果显示,从第2天起,对照组、灵芝高剂量组和中剂量组寻找平台时间呈现逐渐缩短趋势,AD模型组寻找平台时间呈现逐渐增加趋势;第5天,对照组(t=5.607,P=0.000)和灵芝高剂量组(t=2.750,P=0.010)寻找平台时间较模型组明显缩短。空间探索实验结果显示,AD模型组小鼠穿越目标平台所在象限的次数(t=2.452,P=0.025)和在目标象限内滞留时间(t=2.530,P=0.020)明显少于对照组小鼠,穿越目标平台次数较灵芝组高剂量组(t=2.317,P=0.030)和灵芝中剂量组明显减少(t=2.443,P=0.030),且目标象限停留时间较灵芝高剂量组明显减少(t=2.770,P=0.020);灵芝高剂量组小鼠穿越目标平台所在象限的次数(t=2.493,P=0.022)和在目标象限内滞留时间(t=2.683,P=0.015)明显多于安理申组小鼠。Western blot检测结果显示,灵芝高、中剂量组小鼠脑组织中ApoA1表达水平显著高于AD模型组(P<0.01,P<0.05);灵芝高剂量组Aβ-40表达水平显著低于AD模型组(P均<0.05);灵芝高剂量组小鼠脑组织中的Sty1、ApoE、ABCA1水平显著高于模型组(P<0.01,P<0.05)。安理申组(t=30.945,P=0.000)、灵芝中剂量组(t=25.639,P=0.000)和灵芝高剂量组(t=4.689,P=0.001)的血浆IgG水平明显高于对照组。结论灵芝制剂可能改善AD小鼠行为学障碍,促进ApoA1、ApoE和Syt1的表达,抑制Aβ-40蛋白的表达,改善小鼠的自身免疫功能。
其他语种文摘 To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2~(nd) day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5~(th) day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.
来源 中国医学科学院学报 ,2017,39(3):330-335 【核心库】
DOI 10.3881/j.issn.1000-503x.2017.03.006
关键词 灵芝制剂 ; 阿尔茨海默疾病模型 ; 生化因子 ; 免疫化学
地址

1. 中国医学科学院医学实验动物研究所北京协和医学院比较医学中心, 北京, 100021  

2. 美善堂生物科技(深圳)有限公司, 深圳, 518000  

3. 中国医学科学院北京协和医学院基础医学研究所生物化学与分子生物学系, 北京, 100005  

4. 广州中医药大学中药学院, 广州, 510006

语种 中文
文献类型 研究性论文
ISSN 1000-503X
学科 基础医学
文献收藏号 CSCD:6021055

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1 仲丽丽 "药食同源"药材及其有效成分对阿尔茨海默病的作用及机制的研究进展 中国实验方剂学杂志,2022,28(21):235-242
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