阿尔茨海默病异常黑胆质病证结合大鼠模型血清代谢组学研究

发布时间：2018-02-04 17:57

本文关键词： 异常黑胆质证阿尔茨海默病病证结合核磁共振代谢组学　出处：《科技导报》2014年Z2期 　论文类型：期刊论文

【摘要】：为研究阿尔茨海默病(AD)异常黑胆质病证结合大鼠模型血清代谢物的变化,利用代谢组学核磁共振(NMR)技术,根据维吾尔医学理论,采用多因素复合作用建立异常黑胆质证载体动物模型后再予以聚集态Aβ1-40双海马定向注射制备AD异常黑胆质病证结合大鼠模型,收集各组大鼠血清,利用核磁共振波谱(1H-NMR)技术测定核磁共振氢谱,建立模型大鼠血清的代谢指纹谱,运用偏最小二乘判别分析(PLS-DA)法和正交偏最小二乘判别分析(OPLS-DA)法分析研究各组大鼠血清中代谢产物差异。OPLS-DA分析结果显示,各组血清多种代谢组份有显著性差异,单纯痴呆组大鼠血浆中乳酸、糖蛋白、丙酮、极低密度脂蛋白(VLDL)、甲酸和不饱和脂类的含量增加,丙二酸的含量降低;异常黑胆质证组大鼠血清中糖蛋白和β-葡萄糖的含量增多,缬氨酸、酪氨酸、苯丙氨酸和1-甲基组氨酸的含量降低;AD异常黑胆质病证结合组大鼠血浆中的不饱和脂类含量增加,甘氨酸、苯丙氨酸、1-甲基组氨酸、蛋氨酸、丙二酸及β-葡萄糖的含量降低,与正常对照组比较差异有统计学意义(P0.05);与单纯痴呆组大鼠组比较,异常黑胆质证组大鼠血浆中的亮氨酸、缬氨酸、丙氨酸、酪氨酸、α-葡萄糖、β-葡萄糖、肉碱、柠檬酸和不饱和脂类的含量降低。AD异常黑胆质病证结合组大鼠血浆中丙氨酸和丙酮的含量降低,β-葡萄糖和肌酸的含量增加,差异有统计学意义(P0.05);与异常黑胆质证组比较,AD异常黑胆质病证结合组大鼠血浆中α-葡萄糖、β-葡萄糖、肉碱和柠檬酸的含量增加,差异有统计学意义(P0.05)。由此得出,异常黑胆质证与AD的发生、发展有一定的关联性和协同促进作用,AD异常黑胆质病证结合大鼠模型体内糖代谢紊乱和能量代谢障碍,与单纯痴呆模型及异常黑胆质证模型比较,代谢产物及代谢途径在病变过程中发生了演变,AD异常黑胆质病证结合大鼠模型的代谢变化更为复杂。
[Abstract]:In order to study the changes of serum metabolites in rats with AD-abnormal black bile disease syndrome combined with rat model, the metabolomics nuclear magnetic resonance imaging (NMR) technique was used to study the changes of serum metabolites in combination with the Uygur medical theory. The animal model of abnormal black gallbladder syndrome carrier was established by multi-factor compound action, and then the agglomerated A 尾 1-40 bilateral hippocampal injection was used to make AD abnormal black bile disease combined with rat model, and the serum of each group of rats was collected. 1H-NMRs were used to determine the nuclear magnetic resonance (1H-NMRs), and the metabolic fingerprints of the serum of the model rats were established. Partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DAA). Methods the results of OPLS-DA analysis showed that the difference of metabolites in serum of rats in each group was different. The contents of lactate, glycoprotein, acetone, very low density lipoprotein (VLDL), formic acid and unsaturated lipid in plasma of rats with simple dementia were significantly different. The content of malonic acid decreased; The contents of glycoprotein and 尾 -glucose in serum of rats with abnormal black gallbladder syndrome increased, while the contents of valine, tyrosine, phenylalanine and 1-methylhistidine decreased. The content of unsaturated lipids in plasma of AD group was increased, while the contents of glycine, phenylalanine 1-methylhistidine, methionine, malonic acid and 尾 -glucose were decreased. Compared with the normal control group, the difference was statistically significant (P 0.05). Compared with the simple dementia group, the plasma leucine, valine, alanine, tyrosine, 伪 -glucose, 尾 -glucose, carnitine were found in the abnormal black gallbladder syndrome group. The contents of citric acid and unsaturated lipids decreased. The plasma levels of alanine and acetone decreased and 尾 -glucose and creatine increased in AD group. The difference was statistically significant (P 0.05). The levels of 伪 -glucose, 尾 -glucose, carnitine and citric acid in plasma of AD combined group were higher than those of abnormal black gallbladder syndrome group. The difference was statistically significant (P 0.05). It was concluded that abnormal black gallbladder cross-examination and the occurrence and development of AD had certain correlation and synergistic effect. Compared with the dementia model and the abnormal black gallbladder syndrome model, the metabolic products and metabolic pathways have evolved in the pathological process of AD combined with the disorder of glucose metabolism and energy metabolism in the rat model. The metabolic changes were more complicated in AD model combined with the syndrome of black gallbladder disease.
【作者单位】：新疆医科大学附属中医医院神志病科;新疆医科大学维吾尔医学院;
【基金】：国家自然科学基金项目(81060311) 新疆维吾尔自治区教育厅高校科研计划项目(XJEDU2011I28) 乌鲁木齐市科技局科技计划项目(H121323001)
【分类号】：R749.16
【正文快照】： 随着人类寿命的延长,阿尔茨海默病(Alzheimer'sDisease,AD)已成为21世纪老龄化社会严重威胁老年人健康和生命的主要疾病之一。AD是一种常见于老年人的中枢神经系统进行性退行性疾病,以进行性的认知功能损害和记忆力减退、精神行为异常以及生活能力减退等为主要表现。AD属痴呆

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