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(P<0.05);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(P<0.05);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(P<0.05)。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。
To investigate the metabolic characteristics of alzheimer's disease (AD) rat model with abnormal savda syndrome, an abnormal savda rat model with multiple factors is established according to the theory of Uighur traditional medicine, and Aβ1-40 ventricle injection is carried out to establish the alzheimer's disease rat model with abnormal savda syndrome. Then, serum samples from all group rats are analyzed by nuclear magnetic resonance (1H-NMR) spectroscopy (600 MHz), and their spectral profiles are projected by orthogonal projections to latent structures (OPLS-DA) for multivariate statistics. The OPLS-DA analysis shows that compared to the normal group, the pure AD group serum has higher levels of lactic acid, glycoproteins, acetone, VLDL, formic acid and unsaturated lipids, yet a lower level of malonic acid. The abnormal savda syndrome group serum has higher levels of glycoproteins and β-glucose, but lower levels of valine, tyrosine, phenylalanin, and 1-methyl-histidine. The anormal savda syndrome AD group serum has a higher level of unsaturated lipids, but lower levels of glycine, phenylalanine, 1-methyl-histidine, methionine, malonic acid, α-glucose and β-glucose (P<0.05). Compared to the pure AD group, the abnormal savda syndrome group serum has lower levels of leucine, valine, alanine, tyrosine, α-glucose, β-glucose, carnitine, citric acid and unsaturated lipids. The abnormal savda syndrome AD group serum has lower levels of alanine and acetone, but higher levels of β-glucose and creatine (P<0.05). Compared with the abnormal savda syndrome group, the abnormal Savda syndrome AD group serum has higher levels of α-glucose, β-glucose, carnitine and citric acid (P<0.05). It is concluded that the abnormal savda syndrome has certain relevance to the development of alzheimer's disease; compared with the abnormal savda syndrome group and pure AD group, the alerted metabolits and metabolic pathway related with disordered glucose metabolism and energy dysmetabolism have variations during the pathological changing process of disease, and the variation of metabolism in the body of abnormal savda syndrome AD rat is more complex.
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