鹿茸多肽对轻度认知功能障碍模型大鼠海马组织中ADAM10、BACE-1表达的影响
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摘要
目的观察鹿茸多肽对轻度认知功能障碍模型大鼠学习记忆功能及海马组织中解聚素和金属蛋白酶10(A DisintegrinAnd Metalloproteinase 10,ADAM10)、β-淀粉样前体蛋白水解酶1(β-site APP cleavage enzyme-1,BACE-1)表达的影响,探讨鹿茸改善MCI学习记忆障碍的相关作用机制。方法 Wistar大鼠60只随机分为6组,即空白对照组、模型组、阳性对照组、鹿茸多肽高、中、低剂量组,连续给药21 d,末次给药后1 h,腹腔注射氢溴酸东莨菪碱复制MCI大鼠模型。Morris水迷宫观察各组大鼠行为学变化,Elisa法检测各组大鼠海马组织中ADAM10和BACE-1含量,RT-PCR法检测各组大鼠海马组织中m RNA表达水平。结果 Morris水迷宫结果表明,与模型组比较,鹿茸多肽可以延长模型动物的平台穿越次数,增加有效区停留时间(P <0.05或P <0.01)。Elisa检测结果表明,与模型组比较,鹿茸多肽可明显提高模型动物海马组织中的AMAM10、降低BACE-1含量(P <0.05)。RT-PCR检测结果表明,与模型组比较,鹿茸多肽可明显提高模型动物海马组织中的AMAM10、降低BACE-1 mRNA表达水平(P <0.05或P <0.01)。结论鹿茸多肽可以提高氢溴酸东莨菪碱所致的MCI模型大鼠的学习记忆能力,其作用机制与提高海马组织中ADAM10m RNA表达水平,抑制BACE-1 mRNA表达有关。
Objective To observe the effects of Velvet Antler Polypeptide(VAP) on learning and memory function and expression of ADAM10 and BACE-1 in hippocampus of rats with mild cognitive impairment(MCI), and to explore the related mechanism of antler improving MCI learning and memory impairment. Methods Sixty Wistar rats were randomly divided into 6 groups: blank control group, model group, positive control group, high, medium and low dose groups of VAP. The drug was administered continuously for 21 days. One hour after the end of the last administration, intraperitoneal injection of hydrobromine to replicate the scopolamine method. Morris water maze was used to observe the behavioral changes of rats in each group. The content of ADAM10 and BACE-1 in hippocampus of each group was detected by Elisa method. The mRNA expression levels of hippocampus in each group were detected by RT-PCR. Results Morris water maze results showed that compared with the model group, the number of platform crossings and the effective area were increased by VAP(P <0.05 or P <0.01). The results of Elisa showed that VAP could significantly increase the content of ADAM10 and decrease the content of BACE-1(P <0.05). The results of RT-PCR showed that VAP could significantly increase the mRNA level of ADAM10 and decrease the mRNA level of BACE-1(P <0.05 or P <0.01). Conclusion VAP can improve the learning and memory ability of MCI model rats induced by scopolamine hydrobromide. The mechanism of action is related to the increase of ADAM10 m RNA expression in hippocampus and the inhibition of BACE-1 mRNA expression.
Objective To observe the effects of Velvet Antler Polypeptide(VAP) on learning and memory function and expression of ADAM10 and BACE-1 in hippocampus of rats with mild cognitive impairment(MCI), and to explore the related mechanism of antler improving MCI learning and memory impairment. Methods Sixty Wistar rats were randomly divided into 6 groups: blank control group, model group, positive control group, high, medium and low dose groups of VAP. The drug was administered continuously for 21 days. One hour after the end of the last administration, intraperitoneal injection of hydrobromine to replicate the scopolamine method. Morris water maze was used to observe the behavioral changes of rats in each group. The content of ADAM10 and BACE-1 in hippocampus of each group was detected by Elisa method. The mRNA expression levels of hippocampus in each group were detected by RT-PCR. Results Morris water maze results showed that compared with the model group, the number of platform crossings and the effective area were increased by VAP(P <0.05 or P <0.01). The results of Elisa showed that VAP could significantly increase the content of ADAM10 and decrease the content of BACE-1(P <0.05). The results of RT-PCR showed that VAP could significantly increase the mRNA level of ADAM10 and decrease the mRNA level of BACE-1(P <0.05 or P <0.01). Conclusion VAP can improve the learning and memory ability of MCI model rats induced by scopolamine hydrobromide. The mechanism of action is related to the increase of ADAM10 m RNA expression in hippocampus and the inhibition of BACE-1 mRNA expression.
引文
[1]李林.中国阿尔茨海默病研究进展[J].中国药理学与毒理学杂志, 2015, 29(5):765-774.
[2]邢鸿飞.炎症与阿尔茨海默病[J].世界科学, 2018(7):18-20.
[3]CUDABACK E, JORSTAD N L, YANG Y, et al. Therapeutic implications of the prostaglandin pathway in Alzheimer’s disease[J]. Biochem Pharmacol, 2014, 88(4):565-572.
[4]MINOGUEAM,JONESRS,KELLYRJ,etal.Ageassociated dys-regulation of microglial activation is coupled with enhanced blood-brain barrier permeability and pathology in APP/PS1 mice[J]. Neurobiol Aging, 2014, 35(6):1442-1452.
[5]王楠,高晓霞,代子彦,等.鹿茸药效物质基础、药理作用、临床应用及质量控制的研究进展[J].中草药, 2017, 48(22):4784-4789.
[6]彭芳,崔渊博,宋文颖,等.远志提取物对阿尔茨海默病小鼠学习记忆能力的干预效果[J].郑州大学学报(医学版),2017, 52(4):407-412.
[7]YUAN X Z, SUN S, TAN L, et al. The role of ADAM10 in alzheimer’s disease[J].J Alzheimers Dis, 2017, 58(2):303-322.
[8]MARCELLO E, BORRONI B, DI L M, et al. ADAM10 as a therapeutic target for brain diseases:from developmental disorders to Alzheimer’s disease[J]. Xpert Opin Ther Targets,2017, 21(11):1017-1026.
[9]李军,姚静,王国芳,等. IL-33对阿尔茨海默病模型大鼠脑组织内β-淀粉样蛋白的清除作用及其机制[J].吉林大学学报(医学版), 2018, 44(5):908-913.
[10]马福云.补肾方治疗阿尔茨海默病的机制研究[D].北京:北京中医药大学, 2018.
[11]袁佳欣,管丽娜,王梅慧,等.人类间充质干细胞治疗阿尔茨海默病相关调控的研究进展[J].中国实用神经疾病杂志, 2018, 21(13):1494-1498.
[12]秦莉霞,吴倩,徐世军.黄芩抗阿尔茨海默病研究概况[J].药学研究, 2018, 37(8):473-476.
[13]付善玉,徐云龙,赵建军.填精益髓解毒法论治血管性认知障碍[J].长春中医药大学学报, 2016, 32(1):58-60.
[14]王艳玲,赵建军.中医药治疗血管性痴呆研究进展[J].世界中西医结合杂志, 2007, 2(2):118-120.
[15]张锡纯.医学衷中参西录[M].石家庄:河北科学技术出版社,1985:274-275.
[16] PERON R, VATANABE I P, COMINETTI M R, et al. Alphasecretase ADAM10 regulation:insights into Alzheimer’s disease treatment[J]. Pharmaceuticals(Basel). 2018 Jan 29,11(1):pii:E12.
[17]PROXJ,BERNREUTHERC,ALTMEPPENH,etal.Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions[J]. J Neurosci, 2013, 33(32):12915-12928.
[18]董阳婷.氧化应激在β-淀粉样蛋白及氟化物引起的实验性中枢神经损伤病理过程中的作用及其分子机制[D].贵阳:贵州医科大学, 2018.
[19]杨擎,隋欣,石晓征,等.基于Nrf2/Keap1信号通路人参皂苷CK靶向调节Aβ分子机制研究[J].中华中医药杂志,2018, 33(5):1840-1845.
[20]张志辰,温彬宇,高俊峰,等.地黄饮子调节PERK/elF2α通路抑制能量代谢障碍AD小鼠脑内β淀粉样蛋白累积的作用机制[J].中国实验方剂学杂志, 2018, 24(21):91-98.
[2]邢鸿飞.炎症与阿尔茨海默病[J].世界科学, 2018(7):18-20.
[3]CUDABACK E, JORSTAD N L, YANG Y, et al. Therapeutic implications of the prostaglandin pathway in Alzheimer’s disease[J]. Biochem Pharmacol, 2014, 88(4):565-572.
[4]MINOGUEAM,JONESRS,KELLYRJ,etal.Ageassociated dys-regulation of microglial activation is coupled with enhanced blood-brain barrier permeability and pathology in APP/PS1 mice[J]. Neurobiol Aging, 2014, 35(6):1442-1452.
[5]王楠,高晓霞,代子彦,等.鹿茸药效物质基础、药理作用、临床应用及质量控制的研究进展[J].中草药, 2017, 48(22):4784-4789.
[6]彭芳,崔渊博,宋文颖,等.远志提取物对阿尔茨海默病小鼠学习记忆能力的干预效果[J].郑州大学学报(医学版),2017, 52(4):407-412.
[7]YUAN X Z, SUN S, TAN L, et al. The role of ADAM10 in alzheimer’s disease[J].J Alzheimers Dis, 2017, 58(2):303-322.
[8]MARCELLO E, BORRONI B, DI L M, et al. ADAM10 as a therapeutic target for brain diseases:from developmental disorders to Alzheimer’s disease[J]. Xpert Opin Ther Targets,2017, 21(11):1017-1026.
[9]李军,姚静,王国芳,等. IL-33对阿尔茨海默病模型大鼠脑组织内β-淀粉样蛋白的清除作用及其机制[J].吉林大学学报(医学版), 2018, 44(5):908-913.
[10]马福云.补肾方治疗阿尔茨海默病的机制研究[D].北京:北京中医药大学, 2018.
[11]袁佳欣,管丽娜,王梅慧,等.人类间充质干细胞治疗阿尔茨海默病相关调控的研究进展[J].中国实用神经疾病杂志, 2018, 21(13):1494-1498.
[12]秦莉霞,吴倩,徐世军.黄芩抗阿尔茨海默病研究概况[J].药学研究, 2018, 37(8):473-476.
[13]付善玉,徐云龙,赵建军.填精益髓解毒法论治血管性认知障碍[J].长春中医药大学学报, 2016, 32(1):58-60.
[14]王艳玲,赵建军.中医药治疗血管性痴呆研究进展[J].世界中西医结合杂志, 2007, 2(2):118-120.
[15]张锡纯.医学衷中参西录[M].石家庄:河北科学技术出版社,1985:274-275.
[16] PERON R, VATANABE I P, COMINETTI M R, et al. Alphasecretase ADAM10 regulation:insights into Alzheimer’s disease treatment[J]. Pharmaceuticals(Basel). 2018 Jan 29,11(1):pii:E12.
[17]PROXJ,BERNREUTHERC,ALTMEPPENH,etal.Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions[J]. J Neurosci, 2013, 33(32):12915-12928.
[18]董阳婷.氧化应激在β-淀粉样蛋白及氟化物引起的实验性中枢神经损伤病理过程中的作用及其分子机制[D].贵阳:贵州医科大学, 2018.
[19]杨擎,隋欣,石晓征,等.基于Nrf2/Keap1信号通路人参皂苷CK靶向调节Aβ分子机制研究[J].中华中医药杂志,2018, 33(5):1840-1845.
[20]张志辰,温彬宇,高俊峰,等.地黄饮子调节PERK/elF2α通路抑制能量代谢障碍AD小鼠脑内β淀粉样蛋白累积的作用机制[J].中国实验方剂学杂志, 2018, 24(21):91-98.