阿尔茨海默病肾虚证病证结合动物模型的制备及验证
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摘要
目的:制备阿尔茨海默病肾虚证病证结合动物模型,并从行为学、组织形态学、生化指标进行验证,为阿尔茨海默病的中西医动物实验研究提供新的造模方法。方法:通过大鼠双侧海马注射Aβ25-35制造疾病模型,腹腔注射D-半乳糖制造亚急性衰老模拟中医肾虚证。从行为学、病理组织学判断疾病模型;抗氧化能力和HPA轴检验肾虚证模型;补肾名方地黄饮子干预后的各项指标的变化,反向验证病证结合动物模型。结果:造模后大鼠的学习记忆能力显著下降,海马部位出现了神经细胞凋亡,与假手术组比较差异具有统计学意义(P<0.05),说明疾病模型造模成功;模型组大鼠抗氧化能力下降,HPA轴功能虚性亢进(P<0.05),说明衰老已经造成肾虚证证候模型;地黄饮子干预后,以上指标均有一定程度的改善(P<0.05)。结论:阿尔茨海默病肾虚证病证结合动物模型制备成功。
Objective: To establish an animal model of Alzheimer's disease with ‘kidney deficiency' syndrome, and to verify it from behavioral, histomorphological and biochemical indicators, so as to provide a new modeling method for animal experiments of Alzheimer's disease. Methods: Aβ25-35 was injected into the rat hippocampus to make the disease model, and D-galactose was injected intraperitoneally to make subacute senescence of kidney deficiency syndrome. The disease model was judged from behaviourology and histopathology; kidney deficiency syndrome model was tested from antioxidant capacity and HPA axis; according to the changes in various indicators after the intervention of Dihuang Yinzi to verify the model reversely. Results: After modeling, the learning and memory ability of rats decreased significantly, and the neuronal apoptosis in hippocampus appeared. Compared with sham operation group, there was a statistical significance(P<0.05). It indicated that the disease model was successful. The antioxidation ability of the model group was decreased and the function of HPA axis was hyperfunction(P<0.05), indicating that aging has caused the syndrome model of kidney deficiency. After the intervention of Dihuang Yinzi, the above indexes were improved to some extent and were statistically significant(P<0.05). Conclusion: It proved that the modelling of animal models of Alzheimer's disease with ‘kidney deficiency' syndrome was successful.
Objective: To establish an animal model of Alzheimer's disease with ‘kidney deficiency' syndrome, and to verify it from behavioral, histomorphological and biochemical indicators, so as to provide a new modeling method for animal experiments of Alzheimer's disease. Methods: Aβ25-35 was injected into the rat hippocampus to make the disease model, and D-galactose was injected intraperitoneally to make subacute senescence of kidney deficiency syndrome. The disease model was judged from behaviourology and histopathology; kidney deficiency syndrome model was tested from antioxidant capacity and HPA axis; according to the changes in various indicators after the intervention of Dihuang Yinzi to verify the model reversely. Results: After modeling, the learning and memory ability of rats decreased significantly, and the neuronal apoptosis in hippocampus appeared. Compared with sham operation group, there was a statistical significance(P<0.05). It indicated that the disease model was successful. The antioxidation ability of the model group was decreased and the function of HPA axis was hyperfunction(P<0.05), indicating that aging has caused the syndrome model of kidney deficiency. After the intervention of Dihuang Yinzi, the above indexes were improved to some extent and were statistically significant(P<0.05). Conclusion: It proved that the modelling of animal models of Alzheimer's disease with ‘kidney deficiency' syndrome was successful.
引文
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[9]苏芮,韩振蕴,范吉平.Aβ致痴呆老龄大鼠模型海马MARCKS表达变化机制及中药对其调节作用研究.中华中医药杂志,2013,28(12):3512-3515
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[2]邹泉,鲍云鹤,郑坚瑜.环境对阿尔茨海默病病因影响.城市环境与城市生态,2000,13(1):33-35
[3]陈原邻,刘喜明.阿尔茨海默病的中西医治疗进展.世界中医药,2014,9(1):113-116
[4]O'Hare E,Weldon D T,Mantyh P W,et al.Delayed behavioral effects following intranhippocampal injection of aggregated A beta(1-42).Brain Researeh,1999,815(1):1-10
[5]Morimoto K,Yoshimi K,Tonohiro T,et al.Coinjection ofβ-amyloid with ibotenic acid in duces synergistic loss of rat hippocampal neurons.Neuroscience,1998,84(2):479-487
[6]王庆国.以血瘀证为切入点进行中医证候规范及其生物学基础研究.江西中医学院学报,2004,16(5):5-10
[7]赵辉,王健.试论多因素复合制作病证结合动物模型思路.安徽中医学院学报,2001,20(5):57-59
[8]白云静,申洪波,孟庆刚,等.基于复杂性科学的中医学发展取向与方略.中国中医药信息杂志,2005,12(1):2-5
[9]苏芮,韩振蕴,范吉平.Aβ致痴呆老龄大鼠模型海马MARCKS表达变化机制及中药对其调节作用研究.中华中医药杂志,2013,28(12):3512-3515
[10]沈自尹.衰老-生理性肾虚证的HPAT轴分子网络调控研究.中国中西医结合杂志,2004,24(9):841-843