异常黑胆质型UC病证大鼠血清的核磁共振代谢组学

NMR metabonomics of serum in a rat model of abnormal savda disease carrying ulcerative colitis

目的:在维吾尔医学体液论的指导下建立异常黑胆质型溃疡性结肠炎(ulcerative colitis,UC)病证大鼠模型,应用基于核磁共振的代谢组学技术,对UC模型组大鼠、异常黑胆质型UC病证组大鼠以及正常组大鼠血清的代谢组分进行分析并判断差异性小分子标志物.方法:按照维吾尔医学理论知识建立维医异常黑胆质证大鼠模型,在此基础上采用2,4-二硝基氯苯复合乙酸法建立异常黑胆质型UC病证大鼠模型,对其血清进行核磁共振氢谱检测,获得各组大鼠血清中的差异性代谢成分.结果:与正常组相比,UC模型组大鼠血清中乳酸、丙酮、乙酰乙酸、β-羟丁酸、肉碱、丙氨酸、甲酸含量升高,而β-葡萄糖、α-葡萄糖、肌酸、低密度脂蛋白(low density lipoprotein,LDL)、丙酮酸、蛋氨酸、谷氨酰胺含量降低;异常黑胆质型UC病证组大鼠血清中α-酮戊二酸、丙酮、乙酰乙酸、β-羟丁酸、甲酸含量升高,而极低密度脂蛋白(very low density lipoprotein,VLDL)、甲基组氨酸、丙酮酸、谷氨酰胺含量降低.与UC模型组相比,异常黑胆质型UC病证组大鼠血清中乳酸、乙酰乙酸、β-葡萄糖、α-葡萄糖、肌酸、LDL、甲酸的含量升高,而柠檬酸含量降低.结论:UC模型组、异常黑胆质型UC病证组、正常组大鼠血清间存在差异代谢组分;脂代谢紊乱是UC模型组和异常黑胆质型UC病证组大鼠共同的病理生理过程.

AIM： To develop a rat model of abnormal savda disease carrying ulcerative colitis （UC）, and to identify serum markers by applying the nuclear magnetic resonance （NMR）-based metabolomics technology. METHODS： According to the theory of traditional Uyghur medicine, a rat model of abnormal savda syndrome was established, and on this basis, UC was induced with 2,4-dinitrochlorobenzene （DNCB） and acetic acid. ^1H NMR based metabolomics analysis was performed using serum samples from different groups of animals. Biomarkers accounting for the metabolic signature perturbation were then identified. RESULTS： Compared with normal rats, lactate, acetone, acetoacetate, β-hydroxybutyrate, carnitine, alanine, and formic acid were increased, and α-glucose, β-glucose, creatine, low density lipoprotein （LDL）, pyruvate, methionine, and glutamine were reduced in serum of rats with simple UC; α-ketoglutarate, acetone, acetoacetate, β-hydroxybutyrate, and formic acid were increased, and very low density lipoprotein （VLVD）, methyl-histidine, pyruvate, and glutamine were reduced in serum of abnormal savda disease carrying UC rats. Compared with rats with simple UC, lactate, acetoacetate, α-glucose, β-glucose, creatine, LDL, and formic acid were increased, and citric acid was reduced in serum of abnormal savda disease carrying UC rats. CONCLUSION： The metabolites in sera of UC rats, abnormal savda disease carrying UC rats and normal rats are significantly different. Dysregulation of lipid metabolism is the common pathophysiological process of simple UC and abnormal savda disease carrying UC.