Investigation of Evolution Rules of Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Ath- erosclerosis by NMR-based Metabolic Profiling and Metabonomic Approaches / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome.</p><p><b>METHODS</b>Totally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet. ED and XZD were used as drug probes. Blood samples were withdrawn at week 2, 4, and 8 after modeling. Blood lipids, blood rheology, histopathology and metabolomics were detected and analyzed. Results Results of blood lipids and pathology showed hyperlipidemia and early AS rat models were successfully established. At week 2 after modeling, levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) significantly increased, which reached the peak at week 4 and maintained at higher levels at week 8. ED exerted obvious effect in improving TC and LDL-C levels of early models, while XZD could greatly improve levels of TC and LDL-C of late models. Rheological results showed at week 2, there was no significant difference in whole blood viscosity, plasma viscosity, or hematocrit between the model group and the normal group (P > 0.05). At week 4 partial hemorheological indicators (such as plasma viscosity) were abnormal. Till week 8 whole blood viscosity, plasma viscosity, and hematocrit were significantly abnormal (P <0. 05, P < 0.01). As time went by, whole blood viscosity, plasma viscosity, and hematocrit showed gradual increasing tendency in the ED group, while they showed gradual decreasing tendency in the XZD group. Results of metabonomics showed significant difference in spectra of metabolites between the normal group and the model group. As modeling time was prolonged, contents of acetyl glucoprotein and glucose in the model group increased in late stage, which was in. line with results of blood lipids and hemorheology. ED showed more obvious effect in early and mid-term modeling (at week 2 and 4), and increased contents of partial metabolites (such as choline, phosphatidyl choline, glycerophosphocholine), but these changes in the XZD group were consistent with those of the model group. In late modeling (at week 8) XZD showed more obvious effect in improving contents of lactic acid, acetyl glycoprotein, LDL, creatine, choline, and glucose.</p><p><b>CONCLUSIONS</b>ED and XZD not only showed regulatory effects on lipid disorders, but also could improve dysbolism of Chos. In formulas corresponding to syndrome, damp-phlegm was main pathogenesis of hyperlipidema and AS in early and mid stages. Blood stasis syndrome began to occur along with it progressed. Phlegm can result in blood stasis and intermingles with stasis. Phlegm turbidity runs through the whole process.</p>

Metabonomic profile of urine from rats administrated with different treatment period of rifampin / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of rifampin (RFP) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology.</p><p><b>METHODS</b>Thirty-six male Wistar rats were randomly divided into control group, 50 mg/kg RFP group, and 100 mg/kg RFP group, with 12 rats in each group. Rats in each group were given intragastric infusion with a daily dose of 0, 50 mg/kg RFP, and 100 mg/kg RFP for 3, 7, and 14 days, respectively. Then 4 rats in each group were killed on the next day of administration to collect blood samples and liver sample for the determination of blood biochemical indicators and for the pathological analysis of the liver. The urine specimens over 24 hours of each rat were collected before and after each treatment until the rat was killed. 1H nuclear magnetic resonance (1H NMR) spectra of these urine specimens were acquired and subjected to data preprocess and principal component analyses (PCA).</p><p><b>RESULTS</b>The level of serum total bilirubin of the rat administrated with 100 mg/(kg x d) RFP for 7 days was significantly higher than that of control group (P < 0.05). Mild hepatotoxicity to the rat, treated with RFP of higher dosage (100 mg/kg) and longer duration (14 days), was revealed by the traditional histopathological method. The metabonomic spectra of rat urine in different groups differed from each other; a trajectory bias in determination of rat urine by 1H NMR occurred depending on the administration duration. As demonstrated by 1H NMR spectra of urine in rats treated with RFP, the concentration of urinary citrate and 2-oxoglutarate decreased, along with the remarkable increase of the concentrations of urinary taurine and glucose (compared with those of the control group).</p><p><b>CONCLUSIONS</b>Being consistent with the results of traditional toxicity evaluation measurements, metabonomic method is more sensitive. The 1H-NMR metabonomic profile of the rat urine is closely related with the duration of RFP. The hepatic toxicity induced by RFP is related to the reduction of energy metabolism in tricarboxylic acid cycle and the perturbation of glucose and lipid metabolism.</p>

Metabonomic study of blood plasma in the assessment of liver graft function / 中国医学科学院学报

<p><b>OBJECTIVE</b>To access the capability of 1H nuclear magnetic resonance (NMR) -based metabonomics in the evaluation of graft function in the perioperation period of liver transplantation.</p><p><b>METHODS</b>Plasma samples of 15 male primary hepatic carcinoma patients were collected for clinical biochemical analysis and 1H NMR spectroscopy 1 day before operation, 1 day and 1 week after the operation. The NMR data were analyzed using principal component analysis.</p><p><b>RESULTS</b>Metabonomic analysis indicated that, compared with those before operation, blood concentrations of valine, alanine, acetone, succinic acid, glutamine, choline, lactate, and glucose increased significantly 1 day after transplantation. One week later, the levels of lipids and choline increased notably, while those of glucose and amino acids decreased. Principal component analysis showed significant difference between metabolic profiles of plasma samples of variant periods of liver transplantation, due to the variation of the levels of glucose, lipids, lactate, and choline. A good agreement was observed between clinical chemistry and metabonomic data.</p><p><b>CONCLUSIONS</b>Metabonomic analysis can clearly identify the difference between the plasma samples of primary hepatic carcinoma patients at different time during the perioperation period of liver transplantation. It therefore may be a promising new technology in predicting the outcomes of liver transplantation.</p>