Metabonomics Study On Different Syndrome Of Atherosclerosis Model Rats Administrated With Traditional Chinese Medicine Of Tongxinluo

As an important part of systems biology, metabonomics has shown its value for the study of diseases and drug in recent years. In this thesis, we study the essence of atherosclerosis and TCM syndromes, assessment of efficacy of TCM by applying the LC/MS platform. The principal outcomes of this thesis were outlined as follows:Fist, we optimized the pretreatment and analytical methods for urine and plasma samples, and established the optimal conditions for urine and plasma analysis by applying UFLC/MS-IT-TOF. For study of disease, the research subjects are the plasma and urine of atherosclerosis rat model. We studied the plasma and urine metabolic profiling using the principal component analysis (PCA) method. The results showed that the bile acid metabolis and lysophosphatidylcholine (LPC) metabolism were up-regulated and amino acid metabolism was down-regulated. For TCM syndromes, multi-variate statistical method was applied for the study of plasma and urine metabolic profiling of excess fatigue (deficiency of qi) and (depression of qi) depression rats model, it was found that the variation of many metabolic pathways, for examples, energy metabolism, nicotinate and nicotinamide metabolism, lecithin metabolism, arginine metabolism, cholesterol metabolism, tryptophan metabolism, and so on. In addition, the combinational rat model of excess fatigue-atherosclerosis was studied applying the metabonomics method. The results show that the bile acid metabolism was up-reulated, the energy metabolism and amino acid metabolism were all down-regulated in model rats, and excess fatigue may accelerate and aggravate the development of atherosclerosis.A LC/MS-based metabonomic method combinded with hierarchical cluster analysis and similarity method were successfully applied for the evaluation of the preventive effects of Tongxinluo in atherosclerosis, excess fatigue, depression and depression- atherosclerosis rats, and for presuming the possible mechanism. The differences between the effects of Tongxinluo and simvastatin in atherosclerosis, Tongxinluo and ginseng in excess fatigue, Tongxinluo and Allium macrostemon Bunge in depression were compared respectively. The results showed that the Tonxinluo had definite effects in the four refered diseases, and had an equivalent holistic prevebtive effects with simvastatin and Allium macrostemon Bunge in atherosclerosis and depression respectively, but with different mechanism. Ginseng had an advantage of intervention effects in excess fatigue when compared with Tongxinluo. The two TCMs had the preventive effects in excess fatigue by regulating the different metabolic pathways in rats.