Qin Chuan, Wu Shanqiu, Chen Baosheng, Wu Xiaoxian, Qu Kunyao, Liu Junmin, Zhang Guifang, Xu Yanfeng, Shu Shunli, Sun Lihua, Li Yanhong, Zhu Hua, Huang Lan, Ma Chunmei, Xu Yuhuan, Han Yunlin, Lu Yaozeng
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2017 Jun 20;39(3):330-335. doi: 10.3881/j.issn.1000-503X.2017.03.006.
Objective 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 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 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.
目的 评价灵芝制剂对APP/PS-1双转基因阿尔茨海默病(AD)小鼠模型行为、生化及自身免疫参数的影响。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、多奈哌齐组、灵芝中剂量(LZ-M)组和灵芝高剂量(LZ-H)组,每组11只。另外,选取10只4月龄C57BL/6小鼠作为对照组。进行水迷宫试验观察行为变化,采用蛋白质免疫印迹法检测脑组织蛋白表达,用间接免疫荧光法检测自身免疫指标。结果 在定位航行实验中,对照组、LZ-H组和LZ-M组自第2天起找到平台的时间逐渐缩短,AD模型组寻找平台的时间逐渐延长。第5天时,对照组(t=5.607,P=0.000)和LZ-H组(t=2.750,P=0.010)找到平台的时间显著短于AD模型组。在空间探索实验中,AD模型组小鼠穿越目标平台的次数(t=2.452,P=0.025)和在目标象限的停留时间(t=2.530,P=0.020)显著少于/短于对照组;此外,AD模型组穿越目标平台的次数显著少于LZ-H组(t=2.317,P=0.030)和LZ-M组(t=2.443,P=0.030),与LZ-H组相比在目标象限的停留时间显著缩短(t=2.770,P=0.020);LZ-H组穿越目标平台象限的次数(t=2.493,P=0.022)和在目标象限的停留时间(t=2.683,P=0.015)显著高于多奈哌齐组。蛋白质免疫印迹分析显示,LZ-H组和LZ-M组小鼠脑组织中ApoA1的表达显著高于AD模型组(P<0.01,P<0.05);LZ-H组Aβ-40表达显著低于AD模型组(P<0.05);LZ-H组小鼠脑组织中Syt1、ApoE和ABCA1的表达显著高于模型组(P<0.01,P<0.05)。多奈哌齐组(t=30.945,P=0.000)、LZ-M组(t=25.639,P=0.000)和LZ-H组(t=4.689,P=0.001)血浆IgG水平显著高于对照组。结论 灵芝制剂可改善AD模型小鼠的行为障碍,促进ApoA1、ApoE和Syt1的表达,抑制Aβ-40蛋白表达,并改善自身免疫功能。