Biological Basic Research On Qi Deficiency And Blood Stasis Syndrome Based On Metabonomics

Qi and blood theory is one of the core theories of traditional Chinese medicine(TCM).The syndrome differentiation of Qi and blood theory is an important method for clinical treatment of diseases in TCM.Judgment on the body’s functional status based on the prosperity and decay of viscera and Qi and blood is related to the eight-class syndrome differentiation of traditional Chinese medicine and viscera syndrome differentiation.It has formed an important way to recognize diseases in traditional Chinese medicine.Qi deficiency and blood stasis syndrome is a common.symptom of many chronic diseases developing to a certain stage.The decrease of exercise ability such as fatigue and laziness caused by Qi deficiency is a common condition indispensable for clinical diagnosis of Qi deficiency and blood stasis syndrome.At present,there are few metabolomic studies based on syndromes of Qi deficiency and Blood stasis.Metabolomics studies on the syndromes are beneficial to quantify clinical diagnostic indicators,and provide objective evidence for the prevention and detection of diseases.Buyang Huanwu Decoction is composed of seven medicines of astragalus,chuanxiong,angelica,safflower,red peony,peach kernel and dilong.It is a classic prescription of traditional Chinese medicine for the treatment of qi deficiency and blood stasis syndrome.Yiqi Huoxue Granules is the Yiqi Huoxue prescription of the National 973 Program "Research on the Theory of Qi and Blood Based on the Combination of Disease and Syndrome",which is derived from Buyang Huanwu Decoction,and its composition of medicine is completely consistent with Buyang Huanwu Decoction,but Adjustments were made in the ratio of medicine flavor.ObjectiveThe purpose of this study is to explore the common and specific biomarkers of cerebralinfarction and heart failure,which both belong to Qi deficiency and blood stasis syndrome by metabolomic method.Furthermore,from the perspective of metabonomics,to clarify the material basis of this TCM syndrome type,and provide modern index and theoretical basis for differentiation of qi deficiency and blood stasis syndrome.MethodThe purpose of this study is to use metabolomic methods to study patients with cerebral infarction with Qi deficiency and blood stasis syndrome,patients with coronary heart disease and heart failure,and corresponding cerebral infarction rats with qi deficiency and blood stasis syndrome,and ischemic heart failure rats.Divided into four parts:The first and third parts are the metabolomics study of serum samples from patients with cerebral infarction of Qi deficiency and blood stasis syndrome and coronary heart disease.Using metabolomics technology to study the serum of patients with cerebral infarction of qi deficiency and blood stasis syndrome,heart failure in coronary heart disease and patients after administration of Yiqi Huoxue granules,to explore biomarkers related to clinical syndromes and clinical diseases of Qi deficiency and blood stasis syndrome To explain relevant biological functions and provide objective indicators for clinical diagnosis.Through the therapeutic effect of the Chinese medicine compound Yiqi Huoxue Granules on the above-mentioned disease syndromes,it is clear whether it plays a role by regulating the relevant biological metabolic pathways,thereby revealing the mechanism of action of the Chinese medicine.At the same time,if the biomarkers are correlated with the intervention of traditional Chinese medicine,it will also help to further verify the reliability of the biomarkers.The second and fourth parts are systematic metabolomics studies on animal models of cerebral infarction and ischemic heart failure with Qi deficiency and blood stasis syndrome.The cerebral infarction model of Qi deficiency and blood stasis syndrome was established by microsphere-induced multiple cerebral infarction combined with water platform incomplete sleep deprivation,and the rat model of ischemic heart failure was established by sleep deprivation combined with left anterior descending coronary artery ligation.The scope of metabolomics analysis is blood samples or tissue samples,excavating relevant biomarkers,especially those related to energy metabolism and oxidative damage related to the theory of Qi and blood,and observing the changes of corresponding metabolic pathways to verify the disease syndrome.Combining the consistency of animal models and clinical disease syndromes and further revealing the occurrence,development process and mechanism of disease syndromes.Result1.Metabonomics study of patients with cerebral infarction with Qi deficiency and blood stasis syndrome:The results of pattern recognition showed that the placebo group and the drug administration group were significantly separated,and the relevant differences between the two groups were found respectively.The results showed that compared with the model group,the administration group had a significant decrease in the content of Histidine,Glycylproline,Leucine,Gentamicin,Pyroglutamic acid,and Proline,mainly involving changes in metabolic pathways such as lipid metabolism,histidine metabolism,and sphingomyelin metabolism.2.Metabonomics study of rats with cerebral infarction due to qi deficiency and blood stasis syndrome:Multiple cerebral infarctions caused by sleep deprivation combined with microspheres were used to establish a rat model with cerebral infarction due to qi deficiency and blood stasis syndrome.The control group had significant differences.Compared with the normal control group,the model group’s body mass,grip strength,and pulse amplitude decreased significantly,and the weight-bearing swimming time was significantly shortened.The results of metabolomics revealed that the metabolic profiles of the model group and the normal group were significantly different through pattern recognition.21 biomarkers related to cerebral infarction with qi deficiency and blood stasis syndrome were detected,of which 16 biomarkers were subjected to Yiqi Huoxue particles Significant callback.Compared with the sham operation group,the content of Citrulline,Glycylproline,Isobutyryl carnitine,Lysine,Diaminopimelic acid,Ornithine,Asparagine,Linolenoyl lysolecithin in the model group was significantly increased,and the content of Glycylproline,Pyroglutamic acid,Pipecolic acid was significantly reduced,mainly involving energy metabolism and inflammation Reaction and arginine metabolism.Pyroglutamic acid,Pipecolic acid,1-Linoleoyl phosphatidylcholine,Glycylproline,Arachidonyl lysolecithin,7,8-Diaminononanoate were detected in metabolomic studies of cerebral infarction diseases of Qi deficiency and blood stasis syndrome,indicating the establishment of Qi deficiency The animal model of cerebral infarction can basically reflect the pathological state of clinical patients with Qi deficiency cerebral infarction.This model is closely related to clinical.3.Metabolomic study of patients with coronary heart disease and heart failure due to qi deficiency and blood stasis syndrome:The results of pattern recognition showed that the placebo group and the drug administration group were significantly separated,and the relevant differences between the two groups were found.As a result,it was found that the content of Leucine and Isobutyryl carnitine in the administration group was significantly lower than that in the model group,and the content of 18-oxo-nonadecanoic acid was significantly increased,which mainly involved energy metabolism,fatty acid oxidation and phosphocholine metabolism.4.Metabolomics study of ischemic heart failure rats with qi deficiency and blood stasis syndrome:the method of sleep deprivation combined with left anterior descending coronary artery ligation was used to establish ischemic heart failure rats with qi deficiency and blood stasis syndrome.And pulse amplitude decreased,abdominal aortic blood flow velocity decreased,and cardiac function indicators showed that the model was successful,metabolomic results through pattern recognition found that the metabolic profile of the model group and the normal control group was significantly different,and detected 25 blood Among the biomarkers related to stasis syndrome and heart failure,21 biomarkers were significantly corrected by Yiqi Huoxue Granules.Compared with the normal control group,the content of Homocamosine,Creatine,Glutathione,Pyroglutamic acid,Niacinamide,Pyruvic acid,Stearic acid,Pantothenic Acid in the model group was significantly reduced,and the content of Proline,Asymmetric dimethylarginine(ADMA),Alanine,Leucine,Indoleacrylic acid was significantly increased High,mainly related to changes in arginine metabolism,energy metabolism,purine metabolism and fatty acid oxidative metabolism pathways.In the metabolomics study of heart failure disease with qi deficiency and blood stasis syndrome,Leucine and Isobutyryl carnitine were detected in both animal and clinical results,and the two markers were administered in clinical patients and animal models compared with the model group.Downgrade.It shows that the animal model of qi deficiency and heart failure can basically reflect the pathological state of clinical patients with qi deficiency and heart failure.This model is closely related to clinical.5.There are common markers for Qi deficiency and blood stasis syndrome with different syndromes:Screening the four groups of metabolomics results showed that a total of 12 biomarkers appeared more than twice in the four groups,and these common differential metabolites are among the four groups of results Verification with each other confirms its relevance to Qi deficiency and blood stasis syndrome.An analysis of the biological pathways involved in these common differential metabolites found that the biological pathways that are closely related to the development of Qi deficiency and blood stasis include the energy metabolism system and the vascular endothelial system.6.There are specific markers for Qi deficiency and blood stasis syndrome with different syndromes:(1)There are 20 biomarkers for Qi deficiency and blood stasis syndrome cerebral infarction group and Qi deficiency blood stasis syndrome cerebral infarction rat group.There are four diseases that are not shared by the two.In addition,we found that the specific biomarkers of cerebral infarction disease of Qi deficiency and blood stasis syndrome include histidine,which is a precursor of histamine with neuroprotective effect(2)There are a total of 17 biomarkers that are not in the Qi deficiency and blood stasis syndrome heart failure patient group and Qi deficiency and blood stasis syndrome heart failure rat group,including ADMA and muscle that characterize heart failure acid.Conclusion1.The animal model of cerebral infarction with Qi deficiency and blood stasis syndrome established in this study is closely related to patients with clinical Qi deficiency and blood stasis syndrome with cerebral infarction.Their common markers include pyroglutamic acid,homoproline,and glycylproline.6 substances including etc.The animal model of heart failure with Qi deficiency and blood stasis syndrome established in this study is closely related to patients with clinical heart failure with Qi deficiency and blood stasis syndrome.Their common markers are leucine and isobutyl carnitine.Compared with the model group,the drug-administration group in the model had a downward adjustment.2.By comparing the metabolomic results of two different diseases,namely heart failure with Qi deficiency and blood stasis syndrome and cerebral infarction with Qi deficiency and blood stasis syndrome,it was found that the syndrome of Qi deficiency and blood stasis may be closely related to energy metabolism and related metabolic pathways of vascular endothelial system.3.The specific marker of cerebral infarction disease with Qi deficiency and blood stasis syndrome is the neuroprotective histamine precursor substance:histidine;the specific marker of heart failure disease with Qi deficiency and blood stasis syndrome is the asymmetric characterization of cardiac insufficiency Sexual dimethyl arginine and creatine.