天胡荽积雪草苷对SAMP8小鼠学习记忆功能的改善作用  

Effects of asiaticoside from Hydrocotyle sibthorpioides on learning and memory function in SAMP8 mice

作　　者：梁春宏[1] 黄权芳[2] 林兴[1] 黄仁彬[1] 林军[1] 

机构地区：[1]广西医科大学药理学教研室,广西南宁530021 [2]广西中医药大学第一附属医院,广西南宁530023

出　　处：《中国药理学通报》2014年第3期96-100,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81260674);广西自然科学基金(No 2013 GXNSFAA019146)

摘　　要：目的观察天胡荽积雪草苷(asiaticoside from Hydrocotyle sibthorpioides,AHS)对快速老化模型SAMP8小鼠学习记忆功能的影响及其可能机制。方法选用6月龄SAMP8小鼠75只,随机分为SAMP8空白组、阳性药石杉碱甲对照组和AHS低、中、高剂量组,每组15只;另选用6月龄SAMR1小鼠15只作正常对照。各组分别灌胃相应药物3个月后,采用Morris水迷宫法检测小鼠的学习记忆能力,采用Western blot测定Aβ1-42蛋白和可塑性相关蛋白在海马组织的表达水平,采用实时荧光定量PCR测定Aβ相关基因的表达。结果 AHS能明显提高小鼠的学习记忆能力。其机制研究表明,AHS明显降低脑组织Aβ1-42蛋白的含量,抑制Aβ相关基因APP、BACE1和CatB的表达,但提高NEP和IDE的水平;另外,AHS能明显提高突触可塑性相关蛋白包括突触后密度蛋白-95、磷-N-甲基-D-天门冬氨酸受体1、磷酸-钙-钙调素依赖性蛋白激酶Ⅱ、磷酸蛋白激酶A Cβ亚基、蛋白激酶Cγ亚单位、磷酸化CREB和脑源性神经营养因子的表达。结论 AHS能明显改善学习记忆功能,其机制可能与降低脑组织Aβ的形成与沉积、提高突触可塑性相关蛋白的表达有关。Aim To investigate the effect and mecha- nism of asiatieoside from Hydroeotyle sibthorpioides （AHS） on learning and memoy abilities in senescence aceelerated-pronemouse/8 （SAMPS）. Methods Sev- enty five SAMP8 of 6-month-old mice were divided in to 5 groups （15 mice per group）： blank group, hu- perzine A control group, low-, mid- and high-dose AHS-treated groups. In addition, 15 SAMR1 mice of 6-month-old were used as ＂normal aging＂ control. Af- ter treatment with drugs for three months respectively, the learning and memory abilities were detected using a Morris water maze test, and Aβ1 42 and its related pro- teins in the hippoeampus were determined by Western blot. Furthermore, the expression of genes related to Aβ was quantitated by qRT-PCR. Results Treatment with AHS significantly improved the learning and mem- ory abilities, markedly reduced the content and deposi- tion of Aβ by inhibiting the expression of mRNA foramyloid protein precursor, β-site amyloid cleaving en- zyme-1 and eathepsin B. It also promoted the expres- sion of mRNA for neprilysin and insulin degrading en- zyme. In addition, AHS significantly inereased the ex- pression of plasticity-related proteins including postsyn- aptie density-95, phosphor-N-methyl-D-aspartate re- ceptor 1, phospho-ealeium- eahnodulin dependent ki- nase II, phospho-protein kinase A Cβ subunit, protein kinase Cγ subunit, phospho-CREB and brain-derived neurotrophic factor. Conclusion The protective effects of AHS on cognitive deficits were mainly due to its ability to attenuate Aβ protein content and deposi- tion and to promote synaptie plasticity related protein expression.

关 键 词：天胡荽 积雪草苷 石杉碱甲 快速老化小鼠 学习记忆功能 Aβ1-42蛋白 Aβ相关基因 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]