Research On Connection Between Individual Sensitivity To Antihypertensive Drugs And Tcm Syndrome Types In Metabolomics

Objectives:①Research and analyze the difference of endogenous plasma small molecule metabolites between overabundant liver-fire syndrome and phlegm-dampness accumulation syndrome, and identify syndrome-related biomarker cluster.②Research and analyze plasma metabolomic profiling between hypertension group and normal group, analyze abnormality of metabolomics in people with hypertension③Explore the correlation between individual sensitivity to antihypertensive drugs and TCM syndrome types to establish a bridge between these two and metabolome.Methods:119 patients with hypertension, in addition to normal control group (K group) with 25 cases. Hypertension group is divided into amlodipine group (A group) with 59 cases, irbesartan group (B group) with 60 cases. Amlodipine group is divided into drug-sensitive group (E+M) with 29 cases, and non-sensitive group (F+N) with 30 cases. According to TCM syndrome differentiation, amlodipine sensitive group is then divided into abundant liver-fire syndrome group (M group) with 14 cases and phlegm-dampness accumulation syndrome group (E group) with 15 cases, while amlodipine non-sensitive group is divided into abundant liver-fire syndrome group (N group) with 15 cases and phlegm-dampness accumulation syndrome group (F group) with 15 cases. Irbesartan group is separated into drug-sensitive group (G+L) with 30 cases as well as non-sensitive group (H+P) with 30 cases. The former group is then sub-divided into abundant liver-fire syndrome group (L group) with 13 cases and phlegm dampness accumulation syndrome group (G group) with 17 cases, while the later group is divided into hyperactive liver-fire syndrome group (P group) with 16 cases and phlegm dampness accumulation syndrome group (H group) with 14 cases according to TCM syndrome differentiation. The next step is to apply gas chromatography - time of flight mass spectrometry (GC-TOF/MS) to test plasma metabolomic profiling in all groups, and then to compare hyperactive liver-fire syndrome group to phlegm dampness accumulation syndrome group in amlodipine and irbesartan group, amlodipine group to control group, irbesartan group to control group, amlodipine sensitive group to non-sensitive group, irbesartan sensitive group to non-sensitive group, by way of Partial Least Squares-Discriminative Analysis (PLS-DA), so as to obtain each sample's score plot of principal components as well as to analyze and identify similarities and differences of endogenous compounds between groups.Results:①In amlodipine group and irbesartan group, the metabolomic profiling of abundant liver-fire syndrome and phlegm dampness accumulation syndrome can be distinguished by gas chromatography - time of flight mass spectrometry (GC-TOF/MS) metabolomic method, Biomarker cluster associated with abundant liver-fire syndrome group may be higher glucose, xylose associated with glucose metabolism, lactic acid, valine and glycine belonging to amino acid but lower a-linolenic acid and glycerol acid; while biomarker cluster of phlegm dampness accumulation syndrome group may be lower a-linolenic acid and glycerol belonging to lipid but higher valine, glycine,hydroxyproline and S-methyl-L-cysteine.②Amlodipine sensitive group and non-sensitive group have different metabolomic characteristic,10 compounds in amlodipine sensitive group are lower than non-sensitive group (P<0.05). and metabolomic profiling in amlodipine sensitive group exhibits a lower level of glucose metabolism and part of the amino acids.③Irbesartan sensitive group and non-sensitive group also showing different metabolomic characteristic, there are 8 significant different compounds in irbesartan sensitive group and non-sensitive group (P<0.05), the metabolomic profiling of irbesartan sensitive group shows higher amino acids but lower lipide.④Amlodipine sensitive group and phlegm dampness accumulation syndrome group show similar metabolomic profiling——lower level of sugar (glucose) and some amino acids (valine, hydroxyproline), and the same goes with irbesartan sensitive group and abundant liver-fire syndrome group——lower level of amino acids (valine, glycine) and level of lipids.Conclusions:①Plasma metabolomic profiling of abundant liver-fire syndrome and phlegm-dampness accumulation syndrome of hypertension can supply some objective evidence for syndrome differentiation.(2)Hypertension patients have abnormal metabolism of sugar, fat, amino acid during metabolism, so metabolomics takes advantages in researching the pathology of hypertention.③The connection between the sensitivity of anti-hypertensive drug and TCM syndrome types in metabolomics, which can help us use individual thinking to choose antihypertension drugs, and established a bridge between integrative treatment of hypertension.