异常黑胆质成熟剂对移植性宫颈癌(U27)肿瘤模型小鼠血清的代谢组学研究

目的 建立移植性宫颈癌(U27)肿瘤小鼠模型并探讨异常黑胆质成熟剂(Abnormal Savda Munziq,ASMq)对移植性宫颈癌(U27)肿瘤模型小鼠血清代谢的影响。方法 采用核磁共振氢谱(¹H-NMR)技术结合模式识别和正交偏最小二乘判别法(OPLS-DA)进行分析,寻求不同剂量的ASMq以及环磷酰胺(Cyclophosphamide,CY)给药干预后移植性宫颈癌(U27)肿瘤模型小鼠血清中代谢产物的变化以及发生改变的代谢网络途径。结果 与正常对照组比较,移植性宫颈癌(U27)肿瘤模型组小鼠血清中异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、甘氨酸等氨基酸及乳酸、柠檬酸、肌酸和1-甲基组氨酸等代谢物含量明显降低,而低密度脂蛋白(low density lipoprotein,LDL)含量升高,差异有统计学意义(P<0.05)。与移植性宫颈癌(U27)肿瘤模型组比较,环磷酰胺组中亮氨酸、丙氨酸等代谢物含量升高,差异有统计学意义(P<0.05)。与移植性宫颈癌(U27)肿瘤模型组比较,灌胃不同剂量ASMq之后小鼠血清中异亮氨酸、亮氨酸、缬氨酸、丙氨酸、谷氨酰胺等氨基酸含量升高及糖蛋白、柠檬酸、肌酸等代谢物含量也有升高趋势,差异有统计学意义(P<0.05)。结论 ASMq对移植性宫颈癌(U27)肿瘤模型小鼠有一定的抗肿瘤作用,其作用机制可能是不仅调节移植性宫颈癌(U27)肿瘤模型小鼠体内发生紊乱的氨基酸、能量代谢,也可以提高免疫功能,从而实现其预防与治疗肿瘤的作用。     

An magnetic resonance-based plasma metabonomic investigation on abnormal Savda in different complicated diseases

OBJECTIVE： To provide existence of abnormal potential evidence for the Savda, we assessed host metabonomic responses and dynamic changes oc- curring in various diseases using 1H nuclear mag- netic resonance （NMR）-based metabonomics. METHODS： Plasma samples taken from patients with complicated diseases with abnormal Savda （n= 140, including 35 cases each of diabetes, asthma, breast cancer, and cervical carcinoma） and from healthy controls （n=35） were analyzed by ~H NMR （600 MHz）, and the spectral profiles were analyzed by multivariate analysis using orthogonal projec- tion to latent structure with discriminant analysis. RESULTS： Supervised modeling of the data provid- ed very good discrimination between patients and healthy controls. Compared with ,the healthy controls, the patient groups with different disease con- ditions displayed similar metabolic changes, characterized by lower creatine, creatinine, lactate, and amino acid levels （including isoleucine, leucine, va- line, alanine, and 1-methylhistidine） and higher lip- id levels （very low-density lipoproteins and unsatu- rated lipids）. Additionally, cancer patients （breast and cervical） showed decreased myo-inositol, a-glucose, and 13-glucose, and increased pyruvate and carnitine in plasma. CONCLUSION： The data indicate that decreased ox- idative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of complicated diseas- es, which may be related to the formation of abnor- mal Savda.     

Plasma amino acid profiling of cancer patients with abnormal Savda based on high-performance liquid chromatography

OBJECTIVE： To investigate metabolic signatures in plasma of cancer patients with abnormal Savda using plasma-free amino acid profiles, and to evaluate the diagnostic potential of these profiles for the detection and explanation of the mechanisms of different symptoms in traditional Uyghur medicine.METHODS： Plasma samples from cancer patients with abnormal Savda（n=85） or non-abnormal Savda（n=105） and a healthy control group（n=65）were analyzed using high-performance liquid chromatography（HPLC）. Orthogonal projection to latent structures with discriminant analysis was used for the classification and prediction of abnormal Savda, and spectral profiles were subjected to Student＇s t-tests to assess statistical significance.RESULTS： Compared with the healthy group, the levels of aspartic acid, glutamate, glycine, histidine,arginine, threonine, alanine, proline, methionine,isoleucine, leucine and phenylalanine decreased significantly in plasma of cancer patients with abnormal Savda（all P〈0.05）. Serine, cystine, tyrosine,valine and lysine levels showed no significant differences（all P〉0.05）. Compared with non-abnormal Savda syndrome patients, abnormal Savda syndrome patients showed high concentrations of glutamate, serine, valine, isoleucine, leucine and phenylalanine（all P〈0.05）. The remaining plasma amino acids showed no significant differences（all P〉0.05）.CONCLUSION： Plasma-free amino acid profiling has the potential to assist in understanding and determining abnormal Savda. A HPLC-based metabonomic platform could be a powerful tool for the classification of symptoms in traditional medicine.     

An magnetic resonance-based plasma metabonomic investigation on abnormal Savda in different complicated diseases

Objective

To provide potential evidence for the existence of abnormal Savda, we assessed host metabonomic responses and dynamic changes occurring in various diseases using ¹H nuclear magnetic resonance (NMR)-based metabonomics.

Methods

Plasma samples taken from patients with complicated diseases with abnormal Savda (n=140, including 35 cases each of diabetes, asthma, breast cancer, and cervical carcinoma) and from healthy controls (n=35) were analyzed by ¹H NMR (600 MHz), and the spectral profiles were analyzed by multivariate analysis using orthogonal projection to latent structure with discriminant analysis.

Results

Supervised modeling of the data provided very good discrimination between patients and healthy controls. Compared with the healthy controls, the patient groups with different disease conditions displayed similar metabolic changes, characterized by lower creatine, creatinine, lactate, and amino acid levels (including isoleucine, leucine, valine, alanine, and 1-methylhistidine) and higher lipid levels (very low-density lipoproteins and unsaturated lipids). Additionally, cancer patients (breast and cervical) showed decreased myo-inositol, α-glucose, and β-glucose, and increased pyruvate and carnitine in plasma.

Conclusion

The data indicate that decreased oxidative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of complicated diseases, which may be related to the formation of abnormal Savda.