Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Efficacy of Danlou Tablet in the Treatment of Coronary Heart Disease with Phlegm and Blood Stasis Syndrome and Its Effects on Serum Inflammatory Factors

[Objectives] To explore the efficacy of Danlou Tablet( DLT) in the treatment of coronary heart disease( CHD) with phlegm and blood stasis syndrome and its effects on serum inflammatory factors. [Methods]One hundred and ninety-seven patients with CHD and phlegm and blood stasis syndrome in our hospital from January 2016 to January 2018 were selected and randomly divided into two groups: control group( n =98) treated with aspirin plus atorvastatin,and research group( n =99) treated with DLT and aspirin plus atorvastatin for one month. The clinical efficacy and incidence of adverse reactions were observed. Serum secretory phospholipase A2( s PLA2),lipoprotein-associated phospholipase A2( LP-PLA2),oxidized low-density lipoprotein( ox-LDL),monocyte chemoattractant protein-1( MCP-1) and World Health Organization Quality of Life( WHOQOL-100) scores were compared before and after one month of treatment. [Results] The total effective rate was93. 94% in the research group,which was higher than that in the control group( 79. 59%,P < 0. 05);the levels of serum s PLA2,LP-PLA2,ox-LDL and MCP-1 in the research group were lower than those in the control group after one month of treatment( P < 0. 05). There was no statistical significance of the difference in the total incidence of adverse reactions between the research group and the control group( P > 0. 05).After one month of treatment,WHOQOL-100 scores were higher in two groups,which were higher in the research group than that in the control group( P < 0. 05). [Conclusions]DLT can significantly reduce the level of serum inflammatory factors,improve the quality of life in patients with CHD and phlegm and blood stasis syndrome.

Biomedical Mechanisms of Blood Stasis Syndrome of Coronary Heart Disease by Systems Biology Approaches

The prevalence of coronary heart disease （CHD） is increasing, and has been a severe burden on society and family worldwide. New ideas need to be achieved for developing more efficacious and safe therapies to treat CHD. Chinese medicine （CM） uses multicomponent drugs to prevent disease and ameliorate symptoms based on patients＇ different syndromes. The benefit of CM in CHD has recently been proven by increasing clinical evidence. More importantly, linking CM syndrome differentiation and biomedical diagnosis might provide innovative thinking for treating CHD. According to epidemiological investigations, blood stasis syndrome （BSS） is the major type of syndrome in CHD. Investigating the biomedical mechanisms of BSS of CHD is a topic of CM research. Because the holistic perspective of systems biology is well matched with CM, the application of omics techniques and other integrative approaches appears inherently appropriate. A wide range of omics techniques, including transcriptomics and proteomics, have been used in studies of BSS of CHD to search for a common ground of understanding. These approaches could be useful for understanding BSS of CHD from clinical and biological viewpoints. Nevertheless, current studies mainly contain results from a single approach, and they have not achieved the holistic, systematic and integrative concept of system biology. Therefore, we discuss the progress and challenges in exploring the biomedical mechanisms of BSS of CHD by systems biology approaches. With further development of systems biology, a better platform to study BSS of CHD may be provided, and biomarkers for BSS of CHD and therapeutic targets may be found. The study of BSS of CHD by systems biology approaches will also be beneficial for developing personalized treatment for BSS of CHD patients.

Protocol to study the effects of AMPK-mTOR/PINK-Parkin dual signaling pathways on the formation of coronary heart disease showing blood stasis symptom pattern based on traditional Chinese medicine theory of“heart governing blood and vessels”

In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.

Metabolomic Profiling Reveals Distinct Patterns of Tricarboxylic Acid Disorders in Blood Stasis Syndrome Associated with Coronary Heart Disease

Objective： To investigate the underlying metabolomic profiling of coronary heart disease（CHD） with blood stasis syndrome（BSS）. Methods： CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group（n=9） and a control group（n=6）, respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter（LVED）, left ventricular end-diastolic diameter（LVEDd）, ejection fraction（EF）, fractional shortening（FS） and other indicators. Gas chromatography coupled with mass spectrometry（GC-MS） and bioinformatics were applied to analyze spectra of CHD plasma with BSS. Results： The results of hemorheology analysis showed significant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased significantly（P〈0.05）. The echocardiograph results demonstrated that cardiac EF and FS showed significant difference（P〈0.05）, with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters. Conclusion： Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classification of CHD with BSS.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

Association of Platelet-Activating Factor Receptor Gene rs5938(G/T) and rs313152(T/C) Polymorphisms with Coronary Heart Disease and Blood Stasis Syndrome in A Chinese Han Population

Objective: To explore the association of the platelet-activating factor receptor(PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease(CHD) and blood stasis syndrome(BSS) of CHD in Chinese Han population. Methods: A total of 570 CHD patients(299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaP shot technology. The statistical analysis was conducted using a multiple variable logistic regression model. Results: Significant differences were detected in the genotypes frequency distributions of the rs5938(P<0.01), but not the rs313152(P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio(aOR)=0.35, 95% confidence interval(CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD(aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD(aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS(aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS(aOR=1.22, 95% CI: 0.81 to 1.85, P>0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27(95% CI: 0.1 to 0.7, P<0.01). Conclusion: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis

Objective To investigate the correlation of platelet and coagulation function with blood stasis syndrome(BSS)in coronary heart disease(CHD).Methods The protocol for this meta-analysis was registered on PROSPERO(CRD42019129452).PubMed,Excerpta Medica Database(Embase),the Cochrane Library,and China National Knowledge Infrastructure(CNKI)were searched from inception to 1st June,2020.Trials were considered eligible if they enrolled BSS and non-BSS(NBSS)patients with CHD and provided information on platelet and coagulation function.The platelet function,coagulation function,and fibrinolytic activity were compared between the BSS and NBSS groups.Forest plots were generated to show the SMDs or ESs with corresponding 95%CIs for each study.Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.Results The systematic search identified 1,583 articles.Thirty trials involving 10,323 patients were included in the meta-analysis.The results showed that mean platelet volume,platelet distribution width,platelet aggregation rate,platelet P selectin,fibrinogen,plasminogen activator inhibitor-1(PAI-1),thromboxane B2(TXB2),6-keto-prostaglandin F1alpha(6-keto-PGF1α),and TXB2/6-keto-PGF1αwere higher in the BSS group than in the NBSS group(P<0.05 or P<0.01).Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD(P<0.01).The R and K values in thromboelastography and tissue plasminogen activator(t-PA)and t-PA/PAI-1 were lower in the BSS group than in the NBSS group(all P<0.01).No difference was found in the results of platelet count,plateletcrit,maximum amplitude,von Willebrand factor,prothrombin time,thrombin time,international normalized ratio,etc.between groups.Conclusions Increased platelet function,hypercoagulability,and decreased fibrinolytic activity were found among CHD patients with BSS.

Blood Stasis Syndrome of Coronary Heart Disease:A Perspective of Modern Medicine

The medical community as a whole is attempting to start preventive therapy for coronary heartdisease （CHD） patients earlier in life. However, the main limitations of such interventions are drug resistanceand adverse reactions. Additionally, traditional biomarker discovery methods for CHD focus on the behavior ofindividual biomarkers regardless of their relevance. These limitations have led to attempting novel approachesto multi-dimensionally investigate CHD and identify safe and efficacious therapies for preventing CHD. Recently,the benefit of Chinese medicine （CM） in CHD has been proven by increasing clinical evidence. More importantly,linking CM theory with modern biomedicine may lead to new scientific discoveries. According to CM theory,all treatments for patients should be based on patients＇ syndromes. A recent epidemiological investigation hasdemonstrated that blood stasis syndrome （BSS） is the major syndrome type of CHD. BSS is a type of complexpathophysiological state characterized by decreased or impeded blood flow. Common clinical features ofBSS include a darkish complexion, scaly dry skin, and cyanosis of the lips and nails, a purple or dark tonguewith purple spots, a thready and hesitant pulse, and stabbing or pricking pain fixed in location accompaniedby tenderness, mass formation and ecchymosis or petechiae. The severity of BSS is significantly correlatedwith the complexity of coronary lesions and the degree of stenosis, and is an important factor affecting theoccurrence of restenosis after percutaneous coronary intervention. The mechanisms of BSS of CHD patientsshould be investigated from a modern medicine perspective. Although many studies have attempted toexplore the biomedical mechanisms of BSS of CHD, from hemorheological disorders to inflammation andimmune responses, the global picture of BSS of CHD is still unclear. In this article, the current status of studiesinvestigating the biomedical mechanisms of BSS of CHD and future perspectives are discussed.

Diagnostic Accuracy of Chinese Medicine Diagnosis Scale of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease: A Study Protocol

Background Phlegm and blood stasis syndrome(PBSS) is one of the main syndromes in coronary heart disease(CHD). Syndromes of Chinese medicine(CM) are lack of quantitative and easyimplementation diagnosis standards. To quantify and standardize the diagnosis of PBSS, scales are usually applied. Objective: To evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. Methods: Six hundred patients with stable angina pectoris of CHD, 300 in case group and 300 in control group, will be recruited from 5 hospitals across China. Diagnosis from 2 experts will be considered as the "gold standard". The study design consists of 2 phases: pilot test is used to evaluate the reliability and validity, and diagnostic test is used to assess the diagnostic accuracy of the scale, including sensitivity, specificity, likelihood ratio and area under the receiver operator characteristic(ROC) curve. Discussion: This study will evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. The consensus of 2 experts may not be ideal as a "gold standard", and itself still requires further study.(No. ChiCTR-OOC-15006599).

Differential Gene Expression Profiles in Coronary Heart Disease Patients of Blood Stasis Syndrome in Traditional Chinese Medicine and Clinical Role of Target Gene

Objective:To investigate the differential gene expression profiles in coronary heart disease(CHD) patients of blood-stasis syndrome(BSS) by oligonucleotide microarray technique,and the clinical significance of target gene.Methods:Subjects were assigned to CHD patients with BSS(n=8),CHD patients without BSS (n=8),and BSS patients without CHD(n=8) based on coronary angiography and the diagnostic criteria of BSS. The sex- and age-matched healthy volunteers(n=8) were enrolled as the control group.Venous blood s...

Effect of Gualou Xiebai Banxia decoction combined with Danshen Decoction on clinical efficacy of unstable angina with phlegm and blood stasis syndrome

Objective:To observe the clinical efficacy and safety of Gualou Xiebai Banxia decoction combined with Danshen decoction on unstable angina(UA)with phlegm and blood stasis syndrome.Method:Eighty patients with UA were randomly divided into treatment group(40 cases)and control group(40 cases)by random number table.The control group was given conventional western medicine treatment,and the experimental group was given Gualou Xiebai Banxia decoction and Danshen decoction on the basis of the control group.Both groups were treated for 4 weeks.Before and after treatment,the angina attacks,dosage of nitroglycerin,traditional Chinese medicine syndrome score,quality of life score,blood lipid,coagulation index and clinical total efficacy were observed and recorded.Results:After 4 weeks of treatment,the attack times and duration of angina in the two groups were both decreased compared with those before treatment.And the treatment group was more significantly reduced than the control group,the difference was statistically significant(p<0.05);the consumption of nitroglycerin of the treatment group was 90.0%,which was better than 67.5%of the control group,the difference was statistically significant(p<0.05);the total effective rate of the treatment group was 90%,which was better than 65%of the control group,the difference was statistically significant(p<0.05);the traditional Chinese medicine(TCM)syndrome score of the experimental group was lower than that of the control group,the differences was significant(p<0.05).The improvement of low density lipoprotein(LDL-C),total cholesterol(TC)and prothrombin time(PT)in the experimental group was better than that in the control group(p<0.05).During the study,there were no obvious adverse reactions in both groups.Conclusion:Gualou Xiebai Banxia decoction combined with Danshen decoction can effectively relieve the attack of angina and the consumption of nitroglycerin,improve clinical symptoms,regulate blood lipid and blood flow state,and improve the quality of life of patients with UA,with good clinical efficacy and safety.

Research on the Correlation between Platelet Gelsolin and Blood-Stasis Syndrome of Coronary Heart Disease

Objective：To study the distribution of gelsolin in human platelet and plasma,and the association with blood-stasis syndrome（BSS） of coronary heart disease（CHD）.Methods：Sixty patients with CHD（30 in BSS group and 30 in non-BSS group） and 30 healthy subjects（control group） were included in this study.The classification of the syndrome was based on clinical symptoms and signs.Gelsolin concentration in platelet rich plasma（PRP）,platelet poor plasma（PPP）,filamentous actin（F-actin） and group-specific component globulin （Gc-globulin） of PPP were determined by enzyme-linked immunosorbent assay（ELISA）.The fluorescence intensity of CD62p and cytoplasmic calcium（[Ca^（2＋）]_i） in human platelets of patients and healthy persons was measured with flow cytometry.Results：Compared with the control group,gelsolin in PRP of the BSS group increased significantly（P0.01）,while that in PPP of the BSS and non-BSS groups decreased markedly（P0.05）, the CD62p,[Ca^（2＋）]_i of platelet,F-actin,and Gc-globulin of the BSS and non-BSS groups increased significantly （P0.01）.Compared with the non-BSS group,the gelsolin concentration in PRP of BSS group increased significantly（P0.01）,the[Ca^（2＋）]_i of platelet of the BSS group increased markedly（P0.01）,while the F-actin and Gc-globulin of the BSS group had no statistical defference（P0.05）.Conclusions：Gelsolin concentration in PRP was increased and accompanied by the elevated[Ca^（2＋）]_i of platelet in CHD with BSS,while gelsolin in PPP were lowered markedly.We speculate that plasma gelsolin may clear F-actin from circulation,thus resulting in depletion of plasma gelsolin significantly.This,in addition to the increased calcium influx of platelets,may lead to the gelsolin abnormal expression on platelets during the process of BSS in CHD.Therefore,platelet gelsolin may serve as a new potential biomarker and a therapeutic target of BSS in CHD.

Relationship between Platelet Activation Related Factors and Polymorphism of Related Genes in Patients with Coronary Heart Disease of Blood-stasis Syndrome

Objective： To comparatively study the expressive conditions of platelet activation related factors （GPⅠb, GPⅡb-Ⅲa and GMP-140） in healthy subjects and patients with coronary heart disease （CHD） of blood-stasis （BS） or non-blood-stasis （non-BS） syndrome, and to analyze the relationship between the activities of various glycoproteins and the polymorphism of genes. Methods： With case control design adopted, patients with the CHD （40 of BS, 37 of non-BS） and 39 healthy subjects for control, all fitting to the inclusion criteria, were selected in this study. The number of affected coronary branches was recorded by the contrast examination. The mean fluorescence intensity （MFI） of GPⅠb, GPⅡb-Ⅲa, and GMP-140 （CD42b, CD61, CD62p） in patients and healthy persons was measured with flow cytometry, the polymorphism of HPA-3 gene was detected by Taqman probe technique and that of HPA-2 gene was determined by gene sequencing. Results： MFI of CD61 and CD62p was higher in the CHD patients than in the healthy control, which was also higher in patients of BS syndrome than in patients of non-BS syndrome （P〈0.05）; MFI of CD42b was lower in the CHD patients than in the healthy control （P〈0.05）, but showing insignificant difference between BS and non-BS syndrome （P〉0.05）; at the same time, no significant difference of all the above-mentioned three MFI could be found in patients with various numbers of affected coronary branches, neither in patients with different genotypes at GPⅡb HPA-3 and GPⅠb HPA-2 polymorphism loci （P〉0.05）. Conclusion： （1） The activities of GP Ⅱ b-Ⅲa and GMP-140 were obviously increased in the genesis and developing process of CHD and CHD of BS syndrome, and so they could be taken as one of the objective indexes for microscopic diagnosis of BS syndrome. （2） The level of GPⅠb was lower in CHD patients than in healthy persons, but it was not a sensitive indicator for BS syndrome of CHD. （3） Levels of GP Ⅱb-Ⅲa, GPⅠb and GMP-140 were not related with the number of affected coronary branches in CHD patients. （4） The changes in amino-acids expression induced by the two loci brought no significant influence on GPⅠb and GP Ⅱb-Ⅲa activities.

Relationship between Two Blood Stasis Syndromes and Inflammatory Factors in Patients with Acute Coronary Syndrome

Objective： To investigate the relationship between inflammatory factors and two Chinese medicine（CM） syndrome types of qi stagnation and blood stasis（QSBS） and qi deficiency and blood stasis（QDBS） in patients with acute coronary syndrome（ACS）. Methods： Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups： 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1（ICAM-1）, chitinase-3-like protein 1（YKL-40） and lipoprotein-associated phospholipase A2（Lp-PLA2）. Results： Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference（P〉0.05）; ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS（P〈0.05）. Conclusion： Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases.Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs.The study of blood stasis syndrome(BSS)and activated blood circulation of traditional Chinese medicine(TCM)is one of the most active fields where the integration of TCM and western medicine in China has been successful.Activated blood circulation herbs(ABC herbs)of Chinese medicine are often used in the treatment of BSS.Most ABC herbs have antiplatelet and anti-atherosclerosis activity,but knowledge about their targets is lacking.Coronary heart disease(CHD),BSS,and platelet activation are closely related.By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD,platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs.In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.

冠心病心血瘀阻证大鼠心肌组织代谢组学研究

目的研究冠心病心血瘀阻证大鼠心肌组织代谢产物谱,探讨其病证生物学基础。方法SD大鼠随机分为假手术组和模型组,采用冠状动脉左前降支结扎法制备冠心病心血瘀阻证大鼠模型,观察大鼠一般状态,检测舌象色度、心电图、心功能,HE染色、透射电镜观察心肌组织形态及超微结构,用超高效液相色谱-质谱技术检测心肌组织差异代谢物,并对代谢通路进行富集分析。结果与假手术组比较,模型组大鼠舌象色度R、G、B值均显著降低(P<0.05),心电图心率、ST段抬高幅度显著上升(P<0.05),左室射血分数、左室短轴缩短率显著下降(P<0.05),左室收缩末期内径、左室舒张末期内径显著上升(P<0.05);心肌组织结构模糊,有炎性细胞浸润,线粒体肿胀、破裂、溶解,嵴结构断裂减少。代谢组学共鉴定出29个假手术组与模型组差异显著的潜在生物标志物(7个上调、22个下调),主要富集于硫胺素代谢,精氨酸生物合成,嘌呤代谢,氨酰基-tRNA生物合成,丙氨酸、天冬氨酸和谷氨酸代谢,戊糖和葡萄糖醛酸相互转化,糖酵解/糖异生,缬氨酸、亮氨酸和异亮氨酸降解,三羧酸循环,丙酮酸代谢10条代谢通路。结论冠状动脉左前降支结扎法可较好地模拟冠心病心血瘀证病理过程,其病理机制涉及葡萄糖代谢、线粒体能量代谢、氨基酸代谢、蛋白质生物合成、嘌呤代谢等多层次代谢网络紊乱。

基于代谢组学的中药治疗冠心病血瘀证生物标志物分析

目的基于代谢组学探讨中药(复方/单味)治疗不同物种冠心病血瘀证所筛选到的差异代谢物,总结中药干预冠心病血瘀证后的生物标志物及相关代谢通路。方法从中国知网、万方数据库、维普数据库、Embase、PubMed、the Cochrane Library、Web of Science数据库中检索中药(复方/单味)治疗冠心病血瘀证的代谢组学研究。对纳入研究的差异代谢物进行汇总,采用HMDB、PubChem-Subs、KEGG对代谢物进行分子注释,对代谢产物路径可视化采用metPA网络软件进行分析。结果共有8篇文献纳入本研究,计算两个物种中重复出现的代谢物后共统计89个差异代谢物主要参与了132条代谢路径。通过通路拓扑分析并对重复出现的代谢通路进行统计后选出了16条P值小于0.05的代谢通路作为中药(复方/单味)治疗不同物种冠心病血瘀证的代谢通路。对于富集于各条差异性代谢通路上的代谢物,在不同研究中重复筛选到的代谢物包括:苯丙氨酸,谷氨酰胺,甘氨酸,柠檬酸盐,胆碱,肌酸,乳酸,葡萄糖,花生四烯酸。结论各项研究中用于冠心病血瘀证治疗的中药(复方/单味)以血府逐瘀汤、桃红四物汤、养心通脉方、苏合香为代表。基于代谢组学的中药(复方/单味)治疗冠心病血瘀证的生物信息学分析显示其作用机制涉及糖代谢、氨基酸代谢、能量代谢、胆碱代谢、脂肪酸代谢等多个方面,基本的三羧酸循环参与其中。总结了包括乳酸、葡萄糖、柠檬酸、花生四烯酸、肌酸、苯丙氨酸、胆碱、谷氨酰胺以及甘氨酸在内的与冠心病血瘀证证候相关的差异代谢物。

基于病证结合的冠心病动物模型制备研究进展与思考

冠心病的临床研究和动物实验研究一直是心血管领域的常见病。病证结合动物模型体现了中西医结合的理念,不仅有西医的疾病特点,而且借助中医思维用不同实验方法来表现独特的中医证候特点,是中医药研究冠心病预防和治疗的有效工具。文章对常用冠心病中医证候的动物模型建立方法进行总结,并以冠心病痰瘀互结证动物模型为例提出思考。

脉通君安汤治疗气虚血瘀型冠心病心绞痛的临床疗效及转录组学研究

目的观察脉通君安汤治疗气虚血瘀型冠心病心绞痛的临床疗效,并通过转录组学方法初步阐明其可能的作用机制。方法将符合纳入标准的140例气虚血瘀型冠心病心绞痛患者依据随机数字法分为治疗组、对照组各70例,治疗期间对照组脱落3例。对照组予冠心病二级预防西医基础治疗,治疗组在对照组治疗基础上加服脉通君安汤,2组疗程均为8周。治疗前后评估2组患者中医证候积分、加拿大心血管学会(Canadian cardiovascular society,CCS)心绞痛分级、西雅图量表(Seattle angina questionnaire,SAQ)评分、焦虑自评量表(Self-rating anxiety scale,SAS)评分、抑郁自评量表(Self-rating depression scale,SDS)评分及不良反应,并基于性别、年龄、病程相匹配原则选取9例患者治疗前后外周血进行转录组学测序。结果治疗后,2组患者中医证候积分均明显下降(P<0.01),治疗组在改善胸痛、胸闷、气短、神倦乏力及总分方面优于对照组(P<0.05,P<0.01);治疗组CCS心绞痛分级总改善率优于对照组(P<0.05);2组治疗前后SAQ、SAS及SDS评分均显著改善(P<0.01),治疗组SAQ评分改善优于对照组(P<0.05,P<0.01)。转录组学结果显示,治疗前后具有显著差异表达的mRNA有862个,包括509个上调,353个下调;GO分析结果显示差异表达的mRNA生物学过程有666条,主要包括病毒基因表达、翻译启动、RNA分解代谢过程等,细胞组分112条,主要包括黏着斑、核糖体亚基、核斑点等;分子功能有94条,主要包括双链RNA结合、钙黏蛋白结合、转录共调节因子活性等;KEGG分析结果显示差异mRNA富集信号通路包括20条,主要包括甘油磷脂代谢通路、单磷酸腺苷激活的蛋白激酶(AMP-activated protein kinase,AMPK)信号通路、核糖体通路等。结论脉通君安汤能够改善气虚血瘀型冠心病心绞痛患者临床症状,其作用机制为多靶点多通路,可能与甘油磷脂代谢通路、AMPK信号通路、核糖体通路的调节相关。