荔枝核皂苷对老年痴呆大鼠的干预作用研究

摘要/Abstract

摘要： 目的: 建立老年痴呆(Alzheimer's disease, AD)大鼠模型,探讨荔枝核皂苷对AD大鼠的治疗作用及其机制。方法: 50只SD大鼠分为:对照组、模型对照组和低、中、高剂量荔枝核皂苷治疗组,共5组,每组10只;Morris水迷宫实验检测各组大鼠的逃避潜伏时间和平台跨越次数;Western blot实验检测各组脑组织β淀粉样蛋白(β-amyloid protein,Aβ)的表达变化;流式细胞仪检测各组脑组织活性氧(ROS)表达的改变。结果: AD大鼠模型组与对照组比较,逃避潜伏时间出现显著性地延长(P<0.01),平台跨越次数显著性地减少(P<0.01)。荔枝核皂苷治疗后AD大鼠的逃避潜伏时间和平台跨越次数得到显著性地改善(P<0.05)。AD大鼠脑组织Aβ的表达水平显著高于正常对照组,高、中、低剂量荔枝核皂苷治疗组可以剂量依赖性地降低模型鼠脑组织中Aβ的表达水平。对照组、模型对照组、低剂量荔枝核皂苷治疗组、中剂量荔枝核皂苷治疗组、高剂量荔枝核皂苷治疗组ROS表达水平的相对值分别为 6.12±0.61、9.54±1.42、8.33±1.26、7.68±1.14、7.23±0.73,模型组显著高于对照组(P<0.01),荔枝核皂苷治疗可以显著降低模型组脑组织中ROS的表达水平(P<0.05)。结论: 荔枝核皂苷具有抗AD大鼠痴呆的活性,减少AD大鼠脑组织Aβ和ROS的生成是其主要的作用机制。

关键词: 老年痴呆, 荔枝核皂苷, β淀粉样蛋白;, 活性氧

Abstract: AIM: To investigate the activity and mechanisms of lychee seed saponin against rats with senile dementia (AD). METHODS: The 50 AD rats were randomly divided into control group, AD model group, low-dose lychee seed saponin group, medium-dose lychee seed saponin group, and high-dose lychee seed saponin group, respectively. Morris water maze examination was used to detect learning and memory ability. The protein expression was detected by Western blot analysis. The level of reactive oxygen species (ROS) was determined by flow cytometer analysis.RESULTS: The escape latency of rats was significantly increased in AD rats (P<0.01),and the numbers of rats crossing platform was significantly decreased in AD rats (P<0.01). The learning and memory ability were significantly developped by lychee seed saponin treatment. The protein expression of Aβ was significant higher in AD rats than that in normal control. The protein expression of Aβ was decreased in a dose-dependent manner by lychee seed saponin treatment in AD rats. The level of ROS in control group, AD model group, low-dose lychee seed saponin group, medium-dose lychee seed saponin group, and high-dose lychee seed saponin group was 6.12±0.61, 9.54±1.42, 8.33±1.26, 7.68±1.14, and 7.23±0.73, respectively. The level of ROS was significant higher in AD rats than that in normal control. The level of ROS was decreased in a dose-dependent manner by lychee seed saponin treatment in AD rats. CONCLUSION: Lychee seed saponin showed the potent activity against AD rats. The decreasing of Aβ and ROS production may play a key role.

Key words: Senile dementia, Lychee seed saponin, β-amyloid protein(Aβ);, Reactive oxygen species

中图分类号:

R965.2

李娟, 王海涛. 荔枝核皂苷对老年痴呆大鼠的干预作用研究[J]. 中国临床药理学与治疗学, 2012, 17(10): 1098-1102.

LI Juan, WANG Hai-tao. Intervention activity of lychee seed saponin against rats with senile dementia and its mechinisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(10): 1098-1102.

参考文献

[1] Taupin P.Aging and neurogenesis, a lesion from Alzheimer's disease[J]. Aging Dis, 2010, 1(2): 158-168.
[2] Taupin P.Adult neurogenesis, neural stem cells and Alzheimer's disease: developments, limitations, problems and promises[J]. Curr Alzheimer Res, 2009, 6(6): 461-470.
[3] Tam JH, Pasternak SH.Amyloid and Alzheimer's disease: inside and out[J]. Can J Neurol Sci, 2012, 39(3): 286-298.
[4] Tian J, Shi J, Zhang X, et al.Herbal therapy: a new pathway for the treatment of Alzheimer's disease[J]. Alzheimers Res Ther, 2010, 2(5): 30-36.
[5] Ho YS, So KF, Chang RC.Drug discovery from Chinese medicine against neurodegeneration in Alzheimer's and vascular dementia[J]. Chin Med, 2011, 6(1): 15-19.
[6] Alsei HA, Moloudi RA, Sarkaki AR.Effects of treadmill running on midterm memory and swim speed in the rat with Morris water maze test[J]. Brain Res, 2008, 12(1): 72-75.
[7] 王浩, 高允生, 张庆乐, 等. 白花丹参水提物促进小鼠学习记忆作用研究[J]. 医药导报, 2009, 28(2): 173-175.
[8] 陈剑梅, 郭洁文, 徐峰. 荔枝核活性成分提取及药理作用的研究进展[J]. 今日药学, 2011, 21(11): 710-712.
[9] 陈衍斌, 武可泗, 陈建宗. 荔枝核皂苷含量测定方法[J]. 陕西中医学院学报, 2007, 30(3): 45-46.
[10] Gotz J, Eckert A, Matamales M, et al.Modes of Aβ toxicity in Alzheimer's disease[J]. Cell Mol Life Sci, 2011, 68(20): 3359-3375.
[11] Chow VW, Mattson MP, Wong PC, et al.An overview of APP processing enzymes and products[J]. Neuromol Med, 2010, 12(1): 1-12.
[12] Dumont M, Kipiani K, Yu F, et al.Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease[J]. J Alzheimers Dis, 2011, 27(1): 211-223.
[13] Ghosh D, Levault KR, Barnett AJ, et al.A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons[J]. J Neurosci, 2012, 32(17): 5821-5832.
[14] Xu X, Xie H, Wang Y, et al.A-type proanthocyanidins from lychee seeds and their antioxidant and antiviral activities[J]. J Agric Food Chem, 2010, 58(22): 11667-11672.
[15] Sharma M, Gupta YK.Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment[J]. Life Sci, 2001, 68(9):1021-1029.