哮喘异常黑胆质证大鼠模型的生物学标志研究

 为了维医证候研究逐步走向标准化和客观化，采用核磁共振（nuclear magnetic resonance，NMR）为基础的代谢组学技术对哮喘异常黑胆质证动物模型体内代谢变化信息与临床患者进行对比研究，揭示两者之间的异同点。分别选择哮喘异常黑胆质证大鼠模型和临床患者作为研究对象，采集血浆样本，通过NMR测试其氢谱，并采用正交偏最小二乘判别分析法（orthogonalpartial least-squares discriminant analysis，OPLS-DA）进行多变量分析。结果显示，与健康志愿者相比，临床患者血浆中亮氨酸、异亮氨酸、缬氨酸和丙氨酸含量明显降低；与脂代谢相关的极低密度脂蛋白（VLDL）和不饱和脂类在患者体内明显降低，而乙酸、丙酮、乙酰乙酸和肉碱含量明显升高；谷氨酰胺在患者体内明显的升高，而肌酸、肌酸酐、鲨肌醇和乳酸明显下降。对动物模型而言，健康对照组与2种模型组比较，模型组大鼠血浆中与脂代谢相关的代谢物以及乳酸、肉碱和谷氨酰胺含量的变化趋势与临床患者一致，但氨基酸含量的变化相反；异常黒胆质证模型大鼠与哮喘异常黒胆质证模型大鼠相比较，只有丙氨酸和肌酸酐含量在哮喘异常黒胆质证模型大鼠血浆中明显比前者低。研究表明，虽然氨基酸的代谢变化在模型大鼠和临床患者体内有所不同，但是与脂代谢相关的代谢物含量的变化趋势一致。氨基酸代谢的不同可能与模型制作过程中环境的剧烈变化有关。脂代谢相关的代谢物可作为临床患者与动物模型共同的异常黑胆质证代谢标志物。

Metabonomic study of abnormal Savda rat model with asthma

In order to standardize the syndrome of traditional Uyghur medicine, abnormal Savda rat model with asthma is selected as study subject and metabolic changes are investigated in animal model and clinical patient to reveal the similarity and difference between them. Sprague Dawley (SD) rats are subjected to abnormal Savda-producing conditions, followed by induction of asthma. Clinical patients of abnormal Savda with asthma are also selected as study subjects. Serum samples are collected from each test group and analyzed by nuclear magnetic resonance (NMR). Spectral profiles are analyzed by multivariate analysis using orthogonal projection to latent structure with discriminant analysis (OPLS-DA). Results show that compared with healthy controls, leucine, isoleucine, valine, alanine, lipid related metabolites like VLDL, and unsaturated lipids concentration in plasma of patients are decreased, but acetic acid, acetone, acetoacetate and carnitine are significantly increased; glutamate in patients also shows a significant increase while creatine, creatinine, scyllo-inositol and lactate are significantly reduced. For animal models, the change in concentration of lipid related metabolites and lactate, carnitine and glutamine is consistent with the clinical patient, but the amino acid displays an opposite trend. Alanine and creatinine concentrations are higher in plasma of abnormal Savda rat model compared to abnormal Savda with asthma rat model. It is concluded that although the amino acid metabolism in rat model is different from that in clinical patient, their changes of lipid related metabolites contents are highly consistent. Fat related metabolites may be considered biomarkers of abnormal Savda.