姜黄素改善快速老化小鼠学习和记忆及其可能机制

张驰豪  戚双双  周鹏  王琼仨  崔怀瑞  陈世新  孙臣友*

doi:10.3969/j.issn.0529-1356.2013.02.007

解剖学报 ›› 2013, Vol. 44 ›› Issue (2) : 182-188. DOI: 10.3969/j.issn.0529-1356.2013.02.007

神经生物学

姜黄素改善快速老化小鼠学习和记忆及其可能机制

张驰豪¹ 戚双双² 周鹏³ 王琼仨¹ 崔怀瑞³ 陈世新³ 孙臣友^3* .

作者信息 +

Curcumin ameliorates the learning and memory of senescence-accelerated mouse and its possible mechanism

ZHANG Chi-hao¹ QI Shuang-shuang² ZHOU Peng³ WAN Qiong-sa¹ CUI Huai-rui³ CHEN Shi-xin³ SUN Chen-you ^3*

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文章历史 +

摘要

目的通过分析海马内磷酸化的钙/钙调素依赖蛋白激酶Ⅱ（p-CaMKII）的表达，评估姜黄素对快速老化小鼠（SAMP8）学习和记忆的影响。方法选用6月龄雄性快速老化小鼠品系8（SAMP8，48只）和抗-快速老化品系(SAMR1，12只)小鼠进行实验。SAMP8小鼠给予剂量分别为20mg/kg和50 mg/kg体重的姜黄素和花生油灌胃处理，每天1次，持续25d。在第26天，每组中6只小鼠通过Morris 水迷宫做行为学检测；每组中另6只小鼠的左半脑匀浆，通过Western blotting法测定海马细胞膜组分中p-CaMKII的表达；对右半脑进行后固定，通过免疫组织化学方法和吸光度测定，观察和分析p-CaMKII在海马CA3区的分布和表达情况。结果 20 mg/kg和50 mg/kg姜黄素处理组水迷宫任务的逃避潜伏期明显少于SAMP8溶剂对照组小鼠（P＜0.05, P ＜0.01）；50 mg/kg姜黄素处理组小鼠经靶象限的时间与总时间的比值较SAMP8溶剂对照组小鼠增大（ P ＜0.05）。此外，50 mg/kg姜黄素处理组小鼠与SAMP8溶剂对照组相比，明显增加了海马CA3区透明层p-CaMKII的吸光度值和海马膜组分中p-CaMKII蛋白的水平。结论姜黄素通过增加海马p-CaMKII的表达剂量依赖性地减少了SAMP8小鼠的认知缺陷，表明姜黄素对老龄小鼠认知缺陷有一定的治疗作用。

Abstract

Objective The present study is to evaluate the effects of curcumin on the learning and memory of senescence-accelerated mouse prone 8 (SAMP8) and possible mechanisms by analyzing the p-calcium/calmodulin-dependent kinase II (p-CaMKII) expression in the hippocampus. Methods Experiments were performed using 6-month-old male SAMP8 and senescence-accelerated-resistant strain mice (SAMR1). SAMP8 mice were intragastrically administered curcumin at a dose of 20 or 50 mg/kg body weight or fed the same amount of corn oil (SAMP8 treated with vehicle), once a day for 25 consecutive days. Six mice in each group were performed behavior testing by Morris water maze at day 26 (D26) after treatment. The left side of hippocampus from other 6 mice in each group was homogenized and p-CaMKII expressions in hippocampal membrane fraction were measured by Western blotting. The right side of hippocampus was post-fixed and the distribution and expression of p-CaMKII were observed and analyzed in the hippocampal CA3 region by the immunohistochemistry and optical intensity. Results Treatment of curcumin ［20 and 50 mg/(kg •d) i. g.］ significantly reduced the escape latencies of SAMP8 treated with vehicle (P ＜0.05, P＜0.01) in Morris water maze task. SAMP8 treated with 50 mg/kg of curcumin had a much more time swimming in the target quadrant ( P ＜0.05). In addition, 50 mg/kg of curcumin obviously increased the intensity of p-CaMKII in the stratum lucidum of hippocampal CA3, and relative protein level for p-CaMKII/ GADPH in the hippocampal membrane fraction as well. Conclusion The curcumin treatment may attenuate cognitive deficits of SAMP8 mice in a dose-dependent effect by improving the expression of p-CaMKII in the hippocampus. Thus treatment with curcumin may have a potential therapeutic effect for aging-related cognitive dysfunctions.

导出引用

张驰豪戚双双周鹏王琼仨崔怀瑞陈世新孙臣友*. 姜黄素改善快速老化小鼠学习和记忆及其可能机制[J]. 解剖学报. 2013, 44(2): 182-188 https://doi.org/10.3969/j.issn.0529-1356.2013.02.007

ZHANG Chi-hao QI Shuang-shuang ZHOU Peng WAN Qiong-sa CUI Huai-rui CHEN Shi-xin SUN Chen-you* . Curcumin ameliorates the learning and memory of senescence-accelerated mouse and its possible mechanism[J]. Acta Anatomica Sinica. 2013, 44(2): 182-188 https://doi.org/10.3969/j.issn.0529-1356.2013.02.007

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