目的探讨G蛋白耦联受体30(G protein coupled receptor 30,GPR30)激动剂对β淀粉样蛋白(amyloidβ-protein,Aβ)_(1-42)所致小鼠认知功能障碍的治疗作用。方法将72只ICR小鼠随机分为对照组、模型组、阳性对照组、G1低剂量组、G1中剂量组...目的探讨G蛋白耦联受体30(G protein coupled receptor 30,GPR30)激动剂对β淀粉样蛋白(amyloidβ-protein,Aβ)_(1-42)所致小鼠认知功能障碍的治疗作用。方法将72只ICR小鼠随机分为对照组、模型组、阳性对照组、G1低剂量组、G1中剂量组和G1高剂量组。采用双侧海马脑立体定位注射Aβ_(1-42)建立阿尔茨海默病认知功能障碍模型,48h后给予GPR30激动剂G1(1mg/kg、2mg/kg、4mg/kg)。进行Morris水迷宫实验、避暗实验和新物体识别实验测试小鼠的认知能力,采用蛋白质印迹法检测小鼠海马组织中Bcl-2、Bax、caspase-3、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、cAMP效应元件结合蛋白(cAMP response element binding protein,CREB)、p-CREB的表达水平。结果Morris水迷宫实验中,G1高剂量组小鼠的目标象限停留时间百分比和穿越平台次数显著高于模型组(P<0.05);避暗实验中,G1中、高剂量组小鼠的错误次数均显著少于模型组(P<0.05),避暗潜伏期均显著长于模型组(P<0.05);新物体识别实验中,G1中、高剂量组小鼠的识别指数均显著高于模型组(P<0.05)。G1高剂量组小鼠海马组织中的p-CREB/CREB、mBDNF/proBDNF、Bcl-2/Bax的比例显著高于模型组(P<0.05),活化的caspase-3/pro-caspase-3的比例显著低于模型组(P<0.05)。结论GPR30激动剂可通过激活CREB/BDNF通路对Aβ_(1-42)诱导的小鼠认知障碍和神经元凋亡产生保护作用。展开更多
BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheime...BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice w展开更多
基金the National Natural Science Foundation of China, No: 30560189
文摘BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice w
