通天草醇提物对阿尔茨海默病小鼠行为学及海马炎症介质的影响
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摘要
目的探讨通天草醇提物对阿尔茨海默病小鼠学习能力、记忆能力、学习记忆保持能力等行为学及海马炎症介质白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)含量的影响。方法根据随机数字表法将48只雄性C57BL/6小鼠分为六组:模型组、正常组、多奈哌齐组和通天草醇提物高、中、低剂量组,每组8只。采用Aβ_(1-42)(80 pmol/μL)双侧脑室注射的方法诱导阿尔茨海默病模型,各组实验开始每天灌胃1次,多奈哌齐组小鼠给予0.000 92 g/(kg·d)灌胃,通天草醇提物高、中、低剂量组小鼠分别给予3.96、1.98、0.99 g/(kg·d)灌胃,而正常组和模型组小鼠给予生理盐水灌胃,连续治疗35 d。采用Morris水迷宫检测阿尔茨海默病小鼠行为学的改变,酶联免疫吸附法检测阿尔茨海默病小鼠海马IL-1β、TNF-α含量。结果模型组小鼠的逃避潜伏期及游泳距离增加,同时伴有目标停留时间缩短和跨平台次数减少,寻找到水迷宫系统水下平台所需要的时间较长,与正常组比较,模型组小鼠行为学出现明显异常(P<0.05);与正常组比较,模型组海马炎症介质IL-1β、TNF-α水平明显升高,差异有统计学意义(P<0.05);与模型组比较,通天草醇提物高、中剂量组小鼠行为学明显改善,海马IL-1β、TNF-α水平明显降低,差异有统计学意义(P<0.05)。结论通天草醇提物能够改善小鼠的学习能力和记忆障碍,降低炎性反应并缓解血脑屏障损伤,在阿尔茨海默病治疗中发挥重要作用。
Objective To investigate the effects of alcohol extract of Waternut Herb on learning ability, memory ability,learning and memory retention ability of mice with Alzheimer disease, and the effects of interleukin(IL)-1β and tumor necrosis factor-α(TNF-α) in hippocampal inflammation media. Methods Forty-eight male C57 BL/6 mice were divided into six groups according to the random number table method: model group, normal group, Donepezil group, and high,medium, low dose of alcohol extract of Waternut Herb group, with 8 mice in each group. Alzheimer disease model was induced by bilateral intracere broventricular injection of Aβ_(1-42)(80 pmol/μL). Each group of rats was given intragastric administration once a day. The mice in Donepezil group were given 0.000 92 g/(kg·d) by gavage. The mice in the high, medium, low dose of alcohol extract of Waternut Herb group were given 3.96, 1.98, 0.99 g/(kg·d) by gavage, respectively. While the mice in the normal group and model group were given intragastric administration with continuous saline, treatment for 35 days.The Morris water maze was used to detect the changes of behavior in Alzheimer disease mice. The levels of IL-1β and TNF-α in hippocampus of Alzheimer disease mice were determined by enzyme-linked immunosorbent assay. Results The incubation period and swimming distance of mice in the model group were increased. At the same time, the target residence time was shortened and the number of cross-platforms was reduced, it took a long time to find the underwater platform of the water maze system, compared with the normal group, the abnormal behavior in the model group was significantly increased(P < 0.05). Compared with the normal group, the levels of IL-1β and TNF-α of the inflammatory mediators of the hippocampus in model group were significantly increased(P < 0.05). Compared with the model group, the behavior of mice in the high and medium doses of alcohol extract of Waternut Herb group was significantly improved, and the levels of IL-1β and TNF-α in the hippocampus were significantly decreased, the differences were statistically significant(P < 0.05). Conclusion Alcohol extract of Waternut Herb can improve the learning ability and memory impairment of mice, reduce the inflammatory response and relieve blood-brain barrier injury, and plays an important role in the treatment of Alzheimer disease.
Objective To investigate the effects of alcohol extract of Waternut Herb on learning ability, memory ability,learning and memory retention ability of mice with Alzheimer disease, and the effects of interleukin(IL)-1β and tumor necrosis factor-α(TNF-α) in hippocampal inflammation media. Methods Forty-eight male C57 BL/6 mice were divided into six groups according to the random number table method: model group, normal group, Donepezil group, and high,medium, low dose of alcohol extract of Waternut Herb group, with 8 mice in each group. Alzheimer disease model was induced by bilateral intracere broventricular injection of Aβ_(1-42)(80 pmol/μL). Each group of rats was given intragastric administration once a day. The mice in Donepezil group were given 0.000 92 g/(kg·d) by gavage. The mice in the high, medium, low dose of alcohol extract of Waternut Herb group were given 3.96, 1.98, 0.99 g/(kg·d) by gavage, respectively. While the mice in the normal group and model group were given intragastric administration with continuous saline, treatment for 35 days.The Morris water maze was used to detect the changes of behavior in Alzheimer disease mice. The levels of IL-1β and TNF-α in hippocampus of Alzheimer disease mice were determined by enzyme-linked immunosorbent assay. Results The incubation period and swimming distance of mice in the model group were increased. At the same time, the target residence time was shortened and the number of cross-platforms was reduced, it took a long time to find the underwater platform of the water maze system, compared with the normal group, the abnormal behavior in the model group was significantly increased(P < 0.05). Compared with the normal group, the levels of IL-1β and TNF-α of the inflammatory mediators of the hippocampus in model group were significantly increased(P < 0.05). Compared with the model group, the behavior of mice in the high and medium doses of alcohol extract of Waternut Herb group was significantly improved, and the levels of IL-1β and TNF-α in the hippocampus were significantly decreased, the differences were statistically significant(P < 0.05). Conclusion Alcohol extract of Waternut Herb can improve the learning ability and memory impairment of mice, reduce the inflammatory response and relieve blood-brain barrier injury, and plays an important role in the treatment of Alzheimer disease.
引文
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[14]费洪新,周忠光,姜波,等.补阳还五汤对阿尔茨海默病小鼠学习记忆及海马β淀粉样前体蛋白的影响[J].中国实验方剂学杂志,2014,20(20):125-128.
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[16]王睿,费洪新,王琪,等.补阳还五汤对慢性不可预知性温和应激抑郁模型小鼠行为及脑海马CA3区病理形态学影响[J].中国实验方剂学杂志,2017,23(1):158-162.
[17]张英博,费洪新,郭家,等.蝙蝠葛碱对阿尔茨海默病小鼠海马晚期糖基化终产物受体和核转录因子-κB p65的影响[J].中国老年学杂志,2017,37(19):4697-4700.
[18]费洪新,高音,张英博,等.蝙蝠葛苏林碱对阿尔茨海默病小鼠海马的影响和机制[J].中国老年学杂志,2017,37(1):9-12.
[19]费洪新,韩玉生,仲丽丽,等.补阳还五汤对APP/PS1双转基因小鼠学习记忆及海马组织白介素-6水平的影响[J].中国医科大学学报,2014,43(8):677-681.
[20]姜波,费洪新,仲丽丽,等.黄芪多糖对阿尔茨海默病大鼠海马超微结构和低密度脂蛋白受体相关蛋白1水平的影响[J].长春中医药大学学报,2016,3(32):451-454.
[21]费洪新,高音,孙丽慧,等.蝙蝠葛酚性碱对阿尔茨海默病模型小鼠学习记忆和海马的影响[J].中国实验方剂学杂志,2015,21(7):91-94.
[22]魏铁花,李宝龙,刘旭,等.通天草提取物对拟阿尔茨海默氏病模型大鼠学习记忆能力及其海马区组织相关蛋白表达的影响[J].吉林中医药,2013,33(2):179-181.
[23]Zhou ZG,Zhang CY,Fei HX,et al.Phenolic alkaloids from Menispermum dauricum inhibits Bx PC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway[J].Pharmacognosy Magazine,2015,11(44):690-697.
[24]黎冰林,卢鑫,李江超,等.阿尔茨海默病转基因模型Tg2576小鼠血清的代谢组学研究[J].中国实验动物学报,2017,25(2):218-224.
[25]张春梅.补阳还五汤治疗阿尔茨海默病的疗效及对MMSE积分、ADL评分的影响研究[J].中国现代医生,2016,54(31):126-128.
[26]黄雅兰,黄江,宋大强,等.积雪草苷对阿尔茨海默病模型大鼠海马组织中PPAR-γ蛋白表达的影响[J].中国药房,2016,27(34):4791-4793,4794.
[27]赵进,蔡兆伟,管峰,等.阿尔茨海默病与PRNP突变体小鼠动物模型[J].中国实验动物学报,2016,24(5):541-545.
[2]Li M,Guo K,Ikehara S.Stem cell treatment for Alzheimer′s disease[J].Int J Mol Sci,2014,15(10):19226-19238.
[3]Zhang ZX,Zhao RP,Wang DS,et al.Fuzhisan Ameliorates the Memory Deficits in Aged SAMP8 Mice via Decreasing AβProduction and Tau Hyperphosphor rylation of the Hippocampus[J].Neurochem Res,2016,41(11):3074-3082.
[4]Salemme A,Togna AR,Mastrofrancesco A,et al.Anti-inflammatory effects and antioxidant activity of dihydroasparagusic acid in lipopolysaccharide-activated microglial cells[J].Brain Res Bull,2016,120:151-158.
[5]Valero J,Bernardino L,Cardoso FL,et al.Impact of Neuroinflammation on Hippocampal Neurogenesis:Relevance to Aging and Alzheimer′s Disease[J].J Alzheimers Dis,2017,60(1):S161-S168.
[6]Horgusluoglu E,Nudelman K,Nho K,et al.Adult neurogenesis and neurodegenerative diseases:A systems biology perspective[J].Am J Med Genet B Neuropsychiatr Genet,2017,174(1):93-112.
[7]Erickson MA,Banks WA.Blood-brain barrier dysfunction as a cause and consequence of Alzheimer′s disease[J].J Cereb Blood Flow Metab,2013,33(10):1500-1513.
[8]Di Marco LY,Farkas E,Martin C,et al.Is Vasomotion in Cerebral Arteries Impaired in Alzheimer's Disease[J].J Alzheimers Dis,2015,46(1):35-53.
[9]周天,费洪新,田冰,等.通天草水提物对APP/PSI双转基因小鼠学习记忆及海马IL-β和TNF-α水平影响[J].辽宁中医药大学学报,2016,18(3):10-14.
[10]费洪新,韩玉生,杜徽,等.补阳还五汤对阿尔茨海默病小鼠海马形态学和β淀粉样蛋白水平的影响[J].中国实验方剂学杂志,2014,20(23):142-145.
[11]费洪新,周忠光,刘旭,等.补阳还五汤对阿尔茨海默病模型小鼠海马神经元细胞凋亡的影响[J].中国医学装备,2014,11(S2):427-429.
[12]费洪新,周忠光,刘斌.补阳还五汤对阿尔茨海默病小鼠NF-κB p65蛋白的影响[J].中国老年学杂志,2015,35(19):5369-5371.
[13]费洪新,周忠光,韩玉生,等.补阳还五汤对阿尔茨海默病小鼠血脑屏障通透性的影响[J].时珍国医国药,2015,26(5):1028-1031.
[14]费洪新,周忠光,姜波,等.补阳还五汤对阿尔茨海默病小鼠学习记忆及海马β淀粉样前体蛋白的影响[J].中国实验方剂学杂志,2014,20(20):125-128.
[15]Wang F,Liu H,Shen X,et al.The combined treatment of amyloidβ1-42stimulated bone marrow derived dendritic cells plus splenocytes from young mice prevents the developme nt of Alzheimer disease in APPswe/PSENJE 9mice[J].Neurobiol Aging,2015,36(1):111-122.
[16]王睿,费洪新,王琪,等.补阳还五汤对慢性不可预知性温和应激抑郁模型小鼠行为及脑海马CA3区病理形态学影响[J].中国实验方剂学杂志,2017,23(1):158-162.
[17]张英博,费洪新,郭家,等.蝙蝠葛碱对阿尔茨海默病小鼠海马晚期糖基化终产物受体和核转录因子-κB p65的影响[J].中国老年学杂志,2017,37(19):4697-4700.
[18]费洪新,高音,张英博,等.蝙蝠葛苏林碱对阿尔茨海默病小鼠海马的影响和机制[J].中国老年学杂志,2017,37(1):9-12.
[19]费洪新,韩玉生,仲丽丽,等.补阳还五汤对APP/PS1双转基因小鼠学习记忆及海马组织白介素-6水平的影响[J].中国医科大学学报,2014,43(8):677-681.
[20]姜波,费洪新,仲丽丽,等.黄芪多糖对阿尔茨海默病大鼠海马超微结构和低密度脂蛋白受体相关蛋白1水平的影响[J].长春中医药大学学报,2016,3(32):451-454.
[21]费洪新,高音,孙丽慧,等.蝙蝠葛酚性碱对阿尔茨海默病模型小鼠学习记忆和海马的影响[J].中国实验方剂学杂志,2015,21(7):91-94.
[22]魏铁花,李宝龙,刘旭,等.通天草提取物对拟阿尔茨海默氏病模型大鼠学习记忆能力及其海马区组织相关蛋白表达的影响[J].吉林中医药,2013,33(2):179-181.
[23]Zhou ZG,Zhang CY,Fei HX,et al.Phenolic alkaloids from Menispermum dauricum inhibits Bx PC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway[J].Pharmacognosy Magazine,2015,11(44):690-697.
[24]黎冰林,卢鑫,李江超,等.阿尔茨海默病转基因模型Tg2576小鼠血清的代谢组学研究[J].中国实验动物学报,2017,25(2):218-224.
[25]张春梅.补阳还五汤治疗阿尔茨海默病的疗效及对MMSE积分、ADL评分的影响研究[J].中国现代医生,2016,54(31):126-128.
[26]黄雅兰,黄江,宋大强,等.积雪草苷对阿尔茨海默病模型大鼠海马组织中PPAR-γ蛋白表达的影响[J].中国药房,2016,27(34):4791-4793,4794.
[27]赵进,蔡兆伟,管峰,等.阿尔茨海默病与PRNP突变体小鼠动物模型[J].中国实验动物学报,2016,24(5):541-545.