ABSTRACT
This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.
Subject(s)
Rats , Animals , Stroke Volume , Rats, Sprague-Dawley , Ventricular Function, Left , Coronary Disease/drug therapy , MetabolomicsABSTRACT
This study aims to comprehensively summarize articles on the treatment of coronary heart disease angina pectoris with heart blood stasis syndrome(CHD-AP-HBSS) by Guanxin Shutong Capsules(GSC), and comprehensively evaluate the evidence and value of the formula in "6+1" dimensions based on multi-criteria decision analysis(MCDA) model and Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021) with quantitative and qualitative methods, which is expected to highlight the clinical characteristics and advantages of the prescription and serve as a reference for medical and health departments. The dimensions are grade A, B, C, or D. In terms of safety, according to the reports from the spontaneous reporting system of National Center for ADR Monitoring, and literature analysis, GSC mainly results in the adverse reactions of mild or moderate nausea, diarrhea, rash, palpitation, and headache, with favorable prognosis in patients. Nevertheless, severe adverse reactions have been reported after marketing. Thus, additional evidence for its safety should be accumulated, and the current safety is grade B. Meta-analysis proves that GSC in combination with conventional treatment is superior to conventional treatment alone in alleviating AP and symptoms indicated by electrocardiogram(ECG). Therefore, the effectiveness of the medicine is grade A. As for the pharmacoeconomic value, based on the assumption that the per capita disposable income in 2020 is the willingness-to-pay threshold, it is more economical for CHD-AP patients to use GSC combined with conventional treatment than conventional treatment alone. However, as the currently available clinical parameters fail to support the difference in indirect cost between the two groups, the accuracy in the cost of intervention plan needs to be further improved. Therefore, the economy of the prescription is grade B. GSC has been awarded 13 national invention patents and 1 utility model patent, and won a lot of national and provincial patent awards, marking the enterprise service awareness and innovativeness. As a result, it is grade A in aspect of innovation. A questionnaire on the suitability of GSC suggests that publicity and promotion influence patients' choice and thus additional efforts should be made in this aspect. The suitability of this formula is grade B. Both rural and urban residents can afford the medicine for the whole course and the price is close to that of similar Chinese patent medicines. In addition, it is accessible regardless of season and place, so accessibility is grade A. As a Mongolian empirical formula destined to treat heart stabbing pain, it has the effects of activating blood and resolving stasis, dredging channels and activating collaterals, and moving Qi to relieve pain, and boasts the empirical evidence of more than 2 000 human cases. With prominent characteristics of traditional Chinese medicine, it is grade B. Based on the MCDA model and CSC v2.0, GSC is comprehensively class A in the treatment of CHD-AP-HBSS. The result can serve as a reference for basic clinical medication management.
Subject(s)
Humans , Angina Pectoris/drug therapy , Capsules , Coronary Disease/drug therapy , Drugs, Chinese Herbal/adverse effectsABSTRACT
Objective:To observe the effect of Yangxin Tongmaifang （YXTM） on endogenous metabolites in the myocardial tissue of rats with coronary heart disease due to blood stasis based on the metabolomics approach， and to explore its mechanism in the treatment of heart blood stasis syndrome. Method:A rat model of chronic myocardial ischemia due to heart blood stasis was established via the high-fat diet combined with intragastric administration of vitamin D<sub>3</sub> and subcutaneous injection of isoproterenol （ISO）， followed by the intervention with YXTM. The metabolites in the myocardial tissues of rats in the normal group （<italic>n</italic>=8）， model group （<italic>n</italic>=8）， and YXTM group （<italic>n</italic>=8） were detected by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry. The high-throughput metabolomics data were then subjected to multivariate statistical analysis using SIMCA 14.1， and the related metabolic pathways were analyzed with MetaboAnalyst. Result:The myocardial sample points of rats in the three groups were located in different areas of the elliptical confidence interval. The normal group and the model group were completely separated. There existed some crossovers and overlaps between the YXTM group and the normal group. The heart blood stasis syndrome model was proved successfully replicated from the perspective of metabolic profiling， and YXTM had the potential to promote the body to return to a normal state. After the intervention with YXTM， six differential metabolites changed significantly. Such metabolic pathways as valine， leucine， and isoleucine biosynthesis， pantothenate and coenzyme A （CoA） biosynthesis， valine， leucine， and isoleucine degradation， biosynthesis of aminoacyl-transfer RNA synthetases， and purine metabolism were involved. Conclusion:The therapeutic effect of YXTM on heart blood stasis syndrome in rats is related to the improved levels of myocardial endogenous metabolites， and its mechanism involves phospholipid metabolism， amino acid metabolism， energy metabolism， inflammatory response， and platelet activation and aggregation.
ABSTRACT
This article was aimed to study the distribution and effects of apolipoprotein E (ApoE) gene polymorphism of different constitutional types among coronary heart disease (CHD) patients with blood stasis syndrome on vascular endothelial cell (VEC) function. The whole gene sequencing method was used to identify genotypes of ApoE gene among 556 CHD patients with blood stasis syndrome, in order to analyze the relationship between polymorphism of ApoE gene and the level of VEC function. The results showed that the frequency of E3/3 genotype of each physical group was significantly lower than that of the healthy group; and the frequency of E3/4 genotype was significantly higher than that of the healthy group. In addition, the frequency of E3/3 genotype in qi deficiency constitution group was higher than that of blood stasis constitution group and yang deficiency constitution group; but the frequency of E3/4 genotype in blood stasis constitution group and yang deficiency constitution group was higher than that of the qi deficiency constitution group. The levels of ET and ET/NO in each of genotype groups of blood stasis constitution, yang deficiency constitution, qi deficiency constitution of CHD patients with blood stasis syndrome were higher than that of the healthy group (P < 0.05). In the genotype group of blood stasis constitution of CHD patients with blood stasis syndrome, the frequency of E3/4+E4/4 genotype ET was higher than that of other genotypes (P < 0.01). The levels of ET, NO, ET/NO in genotype groups of yang deficiency constitution and qi deficiency constitution of CHD patients with blood stasis syndrome were not significantly different. It was concluded that ApoE genotype E3/4, E3/3 may be the susceptible genotypes of blood stasis syndrome in CHD. There is a certain difference among different constitutional types. CHD with blood stasis syndrome patients, who are the constitution of blood stasis, carrying the ApoE gene polymorphism of E4 allele may have the function of increasing the ET level.
ABSTRACT
This study was aimed to analyze the plasma metabolicomics pathway in rats with heart blood stasis syn-drome. KEGG database was used in the signal pathway analysis. HMDB was used in the analysis of molecular metabolite annotation, enzyme or transporter associated and its related properties. The metPA network software was used in the visualization of metabolite path. The results showed that 9 metabolites involved in 15 metabolic pathways. Among them, the P-value of metabolic pathway of pantothenate and CoA biosynthesis, propanoate metabolism, biosynthesis of unsaturated fatty acids was less than 0.05. It was concluded that the metabolic pathways of pan-tothenate and CoA biosynthesis, propanoate metabolism, biosynthesis of unsaturated fatty acids were involved with the pathological process of rats with heart blood stasis syndrome.
ABSTRACT
Objective To research photoelectric facial blood flow volume characteristic of premature coronary heart disease of heart blood stasis syndrome (HBSS) and phlegm syndrome (PS), and its relation with NO and ET. Methods Patients of premature coronary heart disease of HBSS (36 cases) and PS (35 cases) were selected, with 31 health people as control. The parameter of photoelectric facial blood flow volume was detected with GD-3 photoelectric blood stream plethysm (PBSP) of the facial color-diagnosis. NO was determined by nitrate reductase method and ET was determined by RIA. Results Hb, He, Hf, Hb/Tab and Hf/Hb of HBSS decreased obviously compared with the control (P
ABSTRACT
0.05), but the index of Hf was significantly lower in heart blood stasis syndrome in CHD group than in healthy control group (P
ABSTRACT
Objective To explore the relations among blood lipid,blood rheology and microcirculation of bulbar conjunctiva of model rats of diabetesⅡwith heart blood stasis syndrome.Methods The rats were fed with high fat and caloric feed.Intraperitoneal injection of streptozotocin(STZ)in small dosage was applied to make the model of diabetesⅡ.Then the model of heart blood stasis syndrome was made through introperitoneal injecting dexamethasone and adrenalin.Eight hours after empty stomach,the rats were anaesthetized to measure the microcireulation of bulbar conjunctiva and test the blood lipid and carotid blood rheology.Results The indices of blood lipid,blood rheology and bulbar eonjunetiva microcirculation of model rats were all changed to abnormal,tallying with the changes of cardiovascular complications of diabetes.