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Improving cognitive impairment by Tongxinluo via inhibiting expression of beta-secretase 1/beta-amyloid peptide in experimental vascular dementia

引用

Neural Regeneration Research 2008年第3期3卷 262-266页

作者： Jia Jia Wenbin Zhu Lihui Wang Yun Xu Department of Neurology Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China The State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing 210008 Jiangsu Province China

BACKGROUND： Tongxinluo has been clinically proven to be effective in improving memory and cognitive function in patients with post-stroke vascular dementia. Is the mechanism related to the deposition of beta-amyloid peptide （A β ） in hippocampus？ OBJECTIVE： To observe the effect of Tongxinluo on cognitive impairment in a mouse model with vascular dementia and the changes of A β deposition and β -secretase 1 （BACE1） expression. DESIGN： Randomized controlled study. SETTING： State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School. MATERIALS： The experiment was carried out in the State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2006 to January 2007. A total of 36 healthy Kunming mice, 18 of each gender, were chosen. The study was conducted in accordance with the National Regulations of Experimental Animal Administration, and all animal experiments were approved by the Committee of Experimental Animal Administration of Nanjing University. Tongxinluo was provided by Shijiazhuang Yiling Pharmaceutical Co., Ltd. METHODS： All mice were randomly divided into 6 groups, including naive control （n=6）, sham-operated control （n=6） and experimental groups treated with different doses of Tongxinluo （0.2, 0.4, and 0.6 g/kg/d; n=6 for each group） or vehicle （n=6）. Five groups were subjected to bilateral common carotid arteries （2-VO） occlusion to produce a vascular dementia model （no occlusion was performed in sham-operated group）. The mice in the Tongxinluo treatment groups were intragastricly administered daily with a Tongxinluo suspension （40 g/L in distilled water） at doses of 0.2, 0.4 or 0.6 g/kg/d from day 1 to day 30 post-surgery. The animals in vehicle, sham-operated and naive groups were administered an equal volume of distilled water. MAIN OUTCOME MEASURES： ①Escape latency time

关键词： vascular dementia tongxinluo β -amyloid protein β -secretase 1

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Effect of Modified Wuzi Yanzong Granule(加味五子衍宗颗粒)on Patients with Mild Cognitive Impairment from Oxidative Damage Aspect

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Chinese Journal of Integrative Medicine 2007年第4期13卷 258-263页

作者：王学美富宏刘庚信朱伟李娌杨金霞 Department of Integrated Chinese and Western Medicine of Peking University First Hospital

Objective： To observe the effects of modified Wuzi Yanzong Granule （加味五子衍宗颗粒,WYG） on memory function and the activity of serum superoxide dismutase （SOD）, malondialdehyde （MDA） levels, leukocyte mitochondrial DNA （mtDNA） deletion rate and β-amyloid protein1.28 （A β 1-28 ） in patients with mild cognitive impairment （MCl）. Methods： Thirty-six patients with MCl were selected based on the internationally recognized Petersen＇s criteria, and equally and randomly assigned to two groups. The treated group was treated with WYG and the control group was treated with placebo for 3 months. In addition, 20 healthy subjects were included in the study as the normal control group. Changes of memory function, SOD activity, MDA content, leukocyte mtDNA deletion rate and A β 1-28 content were observed before and after treatment. Results： Compared with the normal control group, the memory quotient and SOD activity in patients with MCl decreased significantly （P 〈 0.01）, while MDA, A β1-28 levels and the leukocyte mtDNA deletion rate increased significantly （P 〈 0.01）. After treatment, levels of memory quotient and serum SOD activity increased while the serum MDA level, leukocyte mtDNA deletion rate and A β 1-28 level decreased in the treated group compared with those before treatment （P〈0.01, P〈0.05）. Meanwhile, leukocyte mtDNA deletion rate and A β 1-28 content in the treated group were all lower than those in the control group （P〈0.05）. Conclusion： WYG could improve memory function in patients with MCl and the therapeutic mechanism is possibly related to the increased activity of anti-oxidase, the improved free radical metabolism and the alleviation of leukocyte mtDNA oxidation damage. WYG shows clinical significance in delaying the progression of MCl.

关键词： modified Wuzi Yanzong Granule mild cognitive impairment memory function oxidative damage β -amyloid protein

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