羟基积雪草苷对D-半乳糖致亚急性衰老模型小鼠学习记忆的影响及机制研究  

Effect of madacassoside on D-galactose-induced learning and memory impairment in mice

作　　者：谭实美 韦玲[1] 黄权芳[2] 林兴[1] 

机构地区：[1]广西医科大学药学院,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》2015年第9期1239-1244,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81260674);广西自然科学基金资助项目(No 2013GXNSFAA019146;2014GXNS FAA118155;2014GXNSFAA118154)

摘　　要：目的探讨天胡荽羟基积雪草苷(madecassoside from hydrocotyle sibthorpioides,MHS)对D-半乳糖致亚急性衰老模型小鼠学习记忆功能的影响及其作用机制研究。方法SPF级昆明♂小鼠75只,随机分为正常组、模型组、MHS低、中、高剂量治疗组。采用D-半乳糖皮下注射建立亚急性衰老模型,利用Morris水迷宫观察小鼠的学习记忆能力;Western blot法测定小鼠海马组织中Aβ1-42蛋白及突触可塑性相关蛋白的水平;RT-PCR法检测Aβ相关基因的表达。结果与模型组比较,MHS能明显降低Aβ1-42蛋白的含量(P<0.05);抑制APP、BACE1和Cat B,同时提高NEP和IDE的表达(P<0.05);增强突触可塑性相关蛋白PSD-95、pNMDAR1、p-Ca MKII、p-PKACβ、PKCγ、p-CREB和BDNF的表达(P<0.05)。结论 MHS能改善小鼠的学习记忆功能,其机制可能与抑制Aβ生成与沉积、增强突触可塑性相关蛋白表达有关。Aim To investigate the protective effect and mechanism of madecassoside from hydrocotyle sibthorpioides（ MHS） on learning and memory impairment induced by D-galactose（ D-gal） in mice. Methods Totally 75 SPF Kunming male mice were divided into normal control group,model group,low-,middleand high-doses of MHS treated groups. The dementia models were induced with D-gal. The learning and memory functions were tested by Morris water maze,the level of Aβ1- 42 and its related proteins in the hippocampus was determined by Western blot,and the expression of Aβ-related genes were determined by RTPCR. Results Compared with model group,MHS markedly decreased the content of Aβ1- 42,inhibited the expression of APP,BACE1 and Cat B,but promoted the expression of NEP and IDE. In addition,AHS significantly increased the expression of plasticity-related proteins including PSD-95,p-NMDAR1,p-Ca MKII,p-PKACβ,PKCγ,p-CREB and BDNF. Conclusions MHS could remarkably ameliorate the learning and memory impairment induced by D-gal in mice,which may be due to its ability to inhibit the Aβ generation and deposition and promote synaptic plasticity related protein expression.

关 键 词：天胡荽 羟基积雪草苷 D-半乳糖 水迷宫 Aβ1-42蛋白 Aβ相关基因 突触可塑性 

分 类 号：R-332[医药卫生] R339.38