BACKGROUND: Modem pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and ...BACKGROUND: Modem pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer's disease (AD) remains unclear. OBJECTIVE: Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS: Ninety healthy Wistar rats of both genders, 15-month-old (n =75) and 3-month-old rats as young controls (n =15), were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd (permission No. Z53021485, Yuxi, Yunan Province, China). Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS: This study was performed at the Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each: model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose (5 mL/kg) every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μ L ibotenic acid (5 g/L) bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension (0.3 mg/kg) was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES: After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency (time-to-platform), number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS: Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test: Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups (both P 〈 0.05). No significant differences in these two indices were measured among the administration groups (all P 〉 0.05). Results of spatial probe test: Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups (P 〈 0.05). There were no significant differences in these two indices among the administration groups (P 〉 0.05). CONCLUSION: PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.展开更多
目的:探讨中药复方银思维对散发性老年痴呆(sporadic Alzhei mer disease,SAD)模型大鼠空间学习记忆功能障碍的作用及其海马神经元超微形态学基础。方法:采用侧脑室注射链脲佐菌素方法制备SAD模型。实验大鼠分为假手术组、模型组、多奈...目的:探讨中药复方银思维对散发性老年痴呆(sporadic Alzhei mer disease,SAD)模型大鼠空间学习记忆功能障碍的作用及其海马神经元超微形态学基础。方法:采用侧脑室注射链脲佐菌素方法制备SAD模型。实验大鼠分为假手术组、模型组、多奈哌齐组和银思维低、中、高剂量组共6组。于造模后第21天开始治疗,各治疗组给予相应的药物灌胃,模型组及假手术组给予等体积的双蒸水灌胃,各组均每日给药1次,共2个月。治疗结束后,以Morris水迷宫定位航行实验及空间探索实验进行大鼠空间学习记忆能力测试,测试完毕处死大鼠并取出海马组织,电子显微镜观察海马神经元超微结构。结果:在定位航行实验中,多奈哌齐组以及银思维低、中、高剂量组与模型组相比,平均逃避潜伏期及总游泳距离均显著缩短(P<0.05或P<0.01)。在空间探索实验中,与模型组相比,各治疗组在目标象限活动时间明显延长(P<0.05或P<0.01)。在多数测试时间段中,多奈哌齐组与银思维低、中、高剂量组组间比较差异均无统计学意义。脑组织海马神经元超微结构观察也证实了药物干预的作用。结论:中药复方银思维能明显改善SAD模型大鼠的空间学习记忆功能障碍。其作用的超微形态学基础可能与保护海马神经元微管结构,防止轴突损伤有关。展开更多
基金Supported by: the National Natural Science Foundation of China, No. 30560189the Grant from Innovation Groupfor Developing Chinese HerbsNew Drugsamong University Talents in Guangxi
文摘BACKGROUND: Modem pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer's disease (AD) remains unclear. OBJECTIVE: Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS: Ninety healthy Wistar rats of both genders, 15-month-old (n =75) and 3-month-old rats as young controls (n =15), were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd (permission No. Z53021485, Yuxi, Yunan Province, China). Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS: This study was performed at the Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each: model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose (5 mL/kg) every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μ L ibotenic acid (5 g/L) bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension (0.3 mg/kg) was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES: After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency (time-to-platform), number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS: Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test: Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups (both P 〈 0.05). No significant differences in these two indices were measured among the administration groups (all P 〉 0.05). Results of spatial probe test: Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups (P 〈 0.05). There were no significant differences in these two indices among the administration groups (P 〉 0.05). CONCLUSION: PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.
文摘目的:探讨中药复方银思维对散发性老年痴呆(sporadic Alzhei mer disease,SAD)模型大鼠空间学习记忆功能障碍的作用及其海马神经元超微形态学基础。方法:采用侧脑室注射链脲佐菌素方法制备SAD模型。实验大鼠分为假手术组、模型组、多奈哌齐组和银思维低、中、高剂量组共6组。于造模后第21天开始治疗,各治疗组给予相应的药物灌胃,模型组及假手术组给予等体积的双蒸水灌胃,各组均每日给药1次,共2个月。治疗结束后,以Morris水迷宫定位航行实验及空间探索实验进行大鼠空间学习记忆能力测试,测试完毕处死大鼠并取出海马组织,电子显微镜观察海马神经元超微结构。结果:在定位航行实验中,多奈哌齐组以及银思维低、中、高剂量组与模型组相比,平均逃避潜伏期及总游泳距离均显著缩短(P<0.05或P<0.01)。在空间探索实验中,与模型组相比,各治疗组在目标象限活动时间明显延长(P<0.05或P<0.01)。在多数测试时间段中,多奈哌齐组与银思维低、中、高剂量组组间比较差异均无统计学意义。脑组织海马神经元超微结构观察也证实了药物干预的作用。结论:中药复方银思维能明显改善SAD模型大鼠的空间学习记忆功能障碍。其作用的超微形态学基础可能与保护海马神经元微管结构,防止轴突损伤有关。