复方丹参片对APP/PS1转基因小鼠焦虑样行为的调节作用  

Regulatory effect of compound Danshen tablet on anxiety-like behavior in APP/PS1 transgenic mice

作　　者：郭海彪[1] 刘旻[1] 李雯珊 李楚源[1] 林建云[1] 蔡越冬[1] 林娟[1] 王德勤[1] 覃仁安[1] 

机构地区：[1]广州白云山和记黄埔中药有限公司,广东广州510515

出　　处：《中国新药与临床杂志》2017年第8期462-467,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：十二五重大新药创制项目(No.2011ZX09201)

摘　　要：目的探讨复方丹参片对阿尔采末病(AD)APP/PS1转基因小鼠焦虑样行为的作用及机制。方法4月龄野生型小鼠(正常组)和APP/PS1转基因小鼠分别灌胃给予溶剂(模型组)或复方丹参片低剂量(180 mg·kg^(-1))、中剂量(360 mg·kg^(-1))、高剂量(720 mg·kg^(-1))和阳性药物舍曲林(15 mg·kg^(-1))60 d后,采用Morris水迷宫实验、新奇抑制摄食实验和高架十字迷宫实验评价复方丹参片对小鼠记忆障碍和焦虑样行为学表现的影响,采用高效液相色谱法(HPLC)和ELISA分别检测小鼠前额皮质、海马和杏仁核γ-氨基丁酸(GABA)和脑源性神经营养因子(BDNF)的含量。结果复方丹参片中、高剂量明显缩短小鼠找到平台的潜伏期,明显增加小鼠原有平台象限的探索时间(P<0.05,P<0.01)。高架十字迷宫试验结果显示,复方丹参片高剂量显著增加APP/PS1转基因小鼠在开臂的时间百分比和进入开臂的次数(P<0.01);新奇抑制摄食实验结果显示,复方丹参片中、高剂量显著缩短APP/PS1转基因小鼠摄食潜伏期(P<0.05,P<0.01)。HPLC和ELISA结果显示,复方丹参片中、高剂量可显著增加APP/PS1转基因小鼠不同脑区如前额皮质、海马和杏仁核GABA和BDNF含量(P<0.05,P<0.01)。结论复方丹参片改善AD转基因小鼠的学习记忆损伤和焦虑样行为,可能与增加脑组织GABA和BDNF水平有关。AIM To investigate the effect of compound Danshen tablet （CDST） on anxietylike behaviors in Alzheimer disease （AD） APP/PS1 transgenic mice. METHODS WT mice and APP/PS1 transgenic mice at the age of 4 months were orally administered with vehicle （control group） or three doses of CDST （180, 360, 720 mg ·kg-1） and positive drug sertraline （15 mg ·kg-1） for 60 days, then the behavioral performance of mice was tested using Morris water maze test, novel suppressed feeding test and elevated plus maze test. High performance liquid chromatography （HPLC） analysis and enzyme linked immnuosorbent assay （ELISA） were used to examine γ-aminobutyric acid （GABA） and brain derived neurotrophic factors （BDNF） level in prefrontal cortex, hippocampus and amygdala of mice. RESULTS CDST 360 and 720 mg .kg-1 significantly shortened the escape latency of mice to platform and exploratory time in platform quadrant （P 〈 0.05, P 〈 0.01）. Elevated plus maze test suggested that CDST 720 mg.kg-1 increased the spend time in open arms and entries to open arms in APP/PS1 transgenic mice （P 〈 0.01）. Novel suppressed feedings test shown that CDST （360, 720 mg-kg-1） could significantly decrease the feeding latency in APP/PS1 transgenic mice （P 〈 0.05, P 〈 0.01）. HPLC and ELISA analysis further suggested that CDST at dose of 360 and 720 mg·kg-1 evidently increased the GABA and BDNF content in profrontal cortex, hippocampus and amygdala of APP/PS1 transgenic mice （P 〈 0.05, P 〈 0.01）. CONCLUSION CDST improves learning and memory deficits and anxiety-like behaviors in AD transgenic mice, which may correlate with increasing GABA and BDNF level in brain.

关 键 词：焦虑 小鼠 转基因 复方丹参片 Γ-氨基丁酸 脑源性神经营养因子 

分 类 号：R285.5[医药卫生—中药学]