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 effects of Yishen Huazhuo Decoction on the learning and memory abilities of hippocampal neurons and the expression of cyclic adenosine monophosphate (CREB), a key protein of hippocampal neurons in SAMP8 mice. Methods Thirty fast-aging mice aged 12 months (SAMP8) were randomly divided into SAMP8 group, donepezil hydrochloride group and Yishen Huazhuo Decoction group. Ten normal aging mice (SAMR1) were used as the control group. Among them, SAMR1 group and SAMP8 group did not interfere with each other. Yishen Huazhuo prescription group received Yishen Huazhuo Fang crude drug 9.62mg / kg, donepezil hydrochloride group received Donepezil hydrochloride 0.01mg / g, Morris water maze test was used to detect the learning and memory of mice in each group The morphological changes of hippocampal neurons in each group were observed by electron microscopy. The expression of CREB protein in hippocampus was detected by Western blot. Results In the navigation experiment, the latency and swimming distance of SAMP8 group mice were significantly longer than that of SAMR1 group (P <0.05). Compared with SAMP8 group mice, latency and swimming time (P <0.05). Compared with the SAMR1 group, the numbers of crossing the target quadrant and t / t in the SAMP8 group were significantly decreased (P <0.05) t / t was significantly higher than that of SAMP8 group (P <0.05), while that of donepezil hydrochloride group was significantly higher than that of SAMP8 group (P <0.05). The synaptic cleft of hippocampal neurons in SAMR1 group was clear under electron microscope, the mitochondrial cristae and membrane were intact, the number of synaptic vesicles was normal and the size was uniform. The synaptic cleft of SAMP8 group was completely fused, blurred, and there was no mitochondria in the pre-synaptic severe edema. The number of synaptic vesicles decreased greatly and the size was not uniform. The synaptic cleft was partially fused in the Yishen Huazhuo prescription group. Pre-edema reduced, the degree of relief for synaptic damage than donepezil hydrochloride group. Compared with SAMR1 group, CREB expression in hippocampus of SAMP8 group was significantly decreased (P <0.05), and Yishen Huazhuo Decoction group and donepezil hydrochloride group could up-regulate CREB expression (P <0.05). Conclusion Yishen Huazhuo Decoction can significantly improve the learning and memory abilities of SAMP8 mice, which may be related to up-regulation of CREB protein expression in hippocampus, protection of synaptic micro-morphology in hippocampal neurons and improvement of neuronal synaptic function.