益肾化浊方对SAMP8小鼠学习记忆能力及海马神经元突触关键蛋白CREB的影响  

Effect of Yishen Huazhuo Prescription on Learning and Memory Ability and Hippocampal Synapses Key Protein CREB of SAMP8 Mice

作　　者：张玉莲[1] 崔远武[1] 周震[1] 张琳琳[1] 宋宛珊[2] 韩文文[1] 

机构地区：[1]天津中医药大学第二附属医院、天津市河北区真理道816号,300150 [2]天津中医药大学

出　　处：《中医杂志》2014年第22期1942-1946,共5页Journal of Traditional Chinese Medicine

基　　金：国家重点基础研究发展计划(“973”计划)资助项目(2010CB530405);国家自然科学基金资助项目(81273940)

摘　　要：目的观察益肾化浊方对SAMP8小鼠学习记忆能力及海马神经元突触关键蛋白环磷腺苷效应元件结合蛋白(CREB)的影响。方法取30只12月龄快速老化小鼠(SAMP8),随机分为SAMP8组、盐酸多奈哌齐组及益肾化浊方组,另取10只正常老化小鼠(SAMR1)作为对照组。其中SAMR1组及SAMP8组不干预,益肾化浊方组给予益肾化浊方生药9.62mg/kg,盐酸多奈哌齐组给予盐酸多奈哌齐0.01mg/g,通过Morris水迷宫实验检测各组小鼠学习记忆能力;通过电镜观察各组小鼠海马神经元突触微观形态学变化;采用Western blot法检测各组小鼠海马组织CREB蛋白的表达。结果在定位航行实验中,SAMP8组小鼠的潜伏时间与游泳总路程比SAMR1组明显延长(P<0.05),与SAMP8组小鼠比较,益肾化浊方组小鼠潜伏时间与游泳总路程明显缩短(P<0.05);空间探索实验中,与SAMR1组比较,SAMP8组小鼠穿越目标象限次数与t/t总明显减少(P<0.05),益肾化浊方组穿越目标象限次数和t/t总较SAMP8组显著增加(P<0.05),而盐酸多奈哌齐组穿越目标象限次数较SAMP8组显著增加(P<0.05)。电镜下SAMR1组小鼠海马神经元突触间隙清晰,突触前线粒体嵴和膜完整,突触小泡数量正常,大小均一。而SAMP8组突触间隙完全融合、模糊不清,突触前重度水肿,未见线粒体,突触小泡数量大量减少,大小不均一,益肾化浊方组突触间隙少部分融合,突触前水肿程度减轻,对于突触损伤的缓解程度优于盐酸多奈哌齐组。与SAMR1组比较,SAMP8组小鼠海马组织CREB表达明显减少(P<0.05),益肾化浊方组与盐酸多奈哌齐组可上调CREB的表达(P<0.05)。结论益肾化浊方可明显改善SAMP8小鼠学习记忆能力,可能与上调海马组织内CREB蛋白的表达,保护海马神经元突触微观形态,进而改善神经元突触功能有关。Objective To observe the effect of Yishen Huazhuo Prescription on learning and memory ability and hippocampal synapses key protein CREB of senescence-accelerated prone mouse （SAMP8） model. Methods Totally 30 SAMP8 mice of 12 months were randomized into SAMP8 group, donepezil group and Yishen Huazhuo Prescrip- tion group. Another 10 senescence-resistant （SAMR1） mice were selected as the control group. The SAMP8 group and the control group were not intervened, Yishen ttuazhuo Prescription group was given Yishen Huazhuo Decoction （9. 62 mg/kg）, and donepezil group was treated with donepezil （0.01 mg/g）. The learning and memory ability was detected with Morris water maze task. The microcosmic morphology of hippocampal neuron synapses of mice in each group was observed under electron microscope. The CREB protein expression in the hippocampus was detected with Western blot method. Results In place navigation test, the latent time and total swimming distance of mice in the SAMP8 group were significantly prolonged as compared with the SAMR1 group （P 〈 0. 05 ）. The latent time and total swimming distance of mice in Yishen Huazhuo Prescription group were apparently shortened as compared with the SAMP$ group （P 〈 0.05 ）. In spatial probe test, the number of mice through target quadrant and t/t in the SAMP8 group were significantly reduced as compared with the SAMR1 group （ P 〈 0. 05 ）. The number of mice through target quadrant and t/t in Yishen Huazhuo Prescription group were significantly increased as compared with the SAMP8 group （P 〈 0. 05）. The number of mice through target quadrant in the donepezil group was apparently increased as com- pared with the SAMP8 group （P 〈 0. 05 ）. Under electron microscope, the brain samples of mice in SAMR1 group showed that synaptic clefts of hippocampal neuron were clear, presynaptic mitochondrial cristae and membrane were complete, and synaptic vesicle count was normal with average size. While in the SAMP8 group, synaptic cleft was in- dis

关 键 词：益肾化浊方 SAMP8鼠 神经元 突触 环磷腺苷效应元件结合蛋白 

分 类 号：R285.5[医药卫生—中药学]