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.

Discussion on the Prevention and Treatment of COVID-19 Causing Lung Disease and Heart Damage Based on Lei Zhongyi's Theory of Intermingled Phlegm,Blood Stasis and Toxin

Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the first consideration should be the protection of cardiac function.Based on the theory of intermingled phlegm,blood stasis and toxin of heart disease put forward by Master Lei Zhongyi,the dialectical treatment thinking of COVID-19 patients from the concept of damage of phlegm,blood stasis and toxin to the heart were discussed.During the diagnosis,critical stage and recovery period of COVID-19,expectorant and blood-activating agents,heat and detoxification agents can be added to promote lung and asthma,free Bizheng and remove blood stasis,calm the heart and calm the mind,and promote the recovery of cardiopulmonary functions.

On the Treatment of Kidney Fibrosis from the Theory of Internal Deficiency of Qi and the Coexistence of Phlegm and Blood Stasis

Traditional Chinese medicine believes that the etiology and pathogenesis of renal fibrosis are characterized by deficiency of the lung,spleen and kidney,and phlegm,blood stasis,dampness and poison.The positive and the evil can influence each other and cause and effect each other,forming the pathological characteristics of the deficiency,the deficiency,the deficiency and the reality.Chinese medicine treatment of the disease has its unique advantages,external and internal injury equal emphasis,correction and dispelling evil and regulation.From the point of view of"deficiency of qi and coexistence of phlegm and blood stasis",the treatment of renal fibrosis can provide theoretical basis for the treatment of the disease.

Clinical study on Chuanxiong Hualiu Mixture in the treatment of blood stasis and phlegm stagnation type of ovarian cyst

Objective:To observe the clinical efficacy of Chuanxiong Hualiu Mixture in the treatment of blood stasis and phlegm stagnation type of ovarian cyst and the effects on physical and chemical indicators.Methods: A total of 80 patients with blood stasis and phlegm stagnation type of ovarian cyst were randomly divided into two groups, research group (n=40) took Chuanxiong Hualiu Mixture, control group (n=40) took Guizhi Fuling Capsule, 3 months was a course of treatment, and the curative effect was compared between two groups.Results:(1) The overall response rate of Chuanxiong Hualiu mixture group after 3 months of treatment was 82.5%, that of Guizhi Fuling Capsule group was 62.5%, the overall response rate of Chuanxiong Hualiu mixture group was higher than that of control group, and the difference was statistically significant;(2) before and after treatment, sex hormone and hemorheology index E2 of both groups decreased significantly, whole blood viscosity, whole blood reduced viscosity and plasma viscosity decreased significantly, the results were statistically significant, but there was no difference between two groups;(3) rank sum test of TCM symptom efficacy between two groups before and after treatment showed that the overall response rate of Chuanxiong Hualiu mixture group was 95%, the overall response rate of Guizhi Fuling Capsule group was 85%, the overall response rate of research group was better than that of control group, and the difference was statistically significant.Conclusion:Chuanxiong Hualiu mixture has good curative effect for the treatment of ovarian cyst, it can effectively improve the patients' blood stasis and phlegm stagnation constitution, and its mechanism of action is associated with lowering estrogen levels and improving hemorrheology.

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.

Professor Jun Li Treating Vascular Dementia from Mutual Conclusion of Phlegm and Blood Stasis

Professor Jun Li believes that the main etiology and pathogenesis of vascular dementia is the combination of phlegm and blood stasis.The symptoms include feeling faint and declined senses in organs of the head,caused by mystery reason.To cure phlegm and blood stasis simultaneously,the therapy promotes the notion of“resolving phlegm and stimulating the circulation of blood,liberate brain orifices,”and treatments with the addition and removal of“Naotaitong Decoction,”which has an amazing clinical curative effect.This paper examines Professor Jun Li’s theoretical foundations and ideas from the syndrome differentiation and treatment of phlegm and blood stasis,systematically examines the curative effect and mechanism of Naotaitong Decoction in the treatment of vascular dementia,and examines the prescription and medication of typical cases for readers,in the hopes of providing guidance to clinical diagnosis and treatment of this disease.

Application of Stone Needle Therapy Based on Blood Stasis Theory in the Treatment of 36 Cases of Knee Osteoarthritis in Early and Middle Stage

Objective:To evaluate the clinical efficacy of stone needle therapy based on blood stasis theory for different traditional Chinese medicine(TCM)syndrome types of patients with knee osteoarthritis in early and middle stage.Methods:Totally 36 patients with knee osteoarthritis were enrolled in the orthopaedic ward between March 2016 and December 2017,and diagnosed as qi stagnation and blood stasis syndrome,cold dampness and stasis syndrome,or phlegm and stasis syndrome according to TCM syndrome differentiation.After treatment,stone needle was used for ironing on the different meridian acupoints according to different syndrome.The efficacy of patients with the above three syndromes was respectively evaluated,and the visual analogue scale(VAS)score and western ontario and mcMaster universities arthritis Index(WOMAC)score of the three groups were calculated before treatment,2 weeks,and 4 weeks after treatment.Results:The effective rates of the three groups were 86.67%,81.82%,and 80.00%,respectively.After 2 weeks and 4 weeks of treatment,the VAS and WOMAC scores of the three groups decreased significantly compared to treatment before(P<0.05).Conclusion:Stone needle therapy for ironing on the acupoints around the knee joint has a good therapeutic effect on knee osteoarthritis of different syndrome types,which is worthy of further application.

Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.

Treatment of Hypertensive Cerebral Hemorrhage by Activating Blood Circulation to Remove Stasis

The treatment of hy-pertensive cerebral hemorrhage(HCH)by activatingblood circulation to removestasis(ABCRS)is a newtherapeutic approach,which is initiated by clinical specialists of TCM andintegrative Chinese andwestern medicine.Al-though it is not a flawless

Clinical observation of Jiangzhi Hugan Recipe combined with rosuvastatin calcium tablets in the treatment of non-alcoholic fatty liver disease

Objective:To investigate the influence of integrated traditional Chinese and Western medicine on the related indexes and TCM syndrome scores of patients with non-alcoholic fatty liver disease.Methods: A total of 128 patients with non-alcoholic fatty liver disease who were admitted to our department from January 2017 to May 18, 2017 were enrolled in the study. According to the hospital admission record number, they were randomly divided into treatment groups (64 cases). and the control group (64 cases). The control group was treated with rosuvastatin calcium tablets. The treatment group was treated with Jiangzhi Fanggan Recipe on the basis of the control group. The treatment was performed for 10 d for a total of 3 courses. Comparison of liver function, blood lipids, insulin resistance index (HOMA-IR), iris (Irisin), superoxide dismutase (SOD), malondialdehyde (MDA), body mass index (BMI), waist circumference (WC), Liver/spleen CT ratio and TCM syndrome scores.Results: The curative effect of TCM symptom in the treatment group (82.82%) was significantly higher than that in the control group (65.62%), and the difference was statistically significant. There was no difference between the two groups before treatment. Compared with before treatment, the levels of each index were significantly improved after treatment, and the improvement of the treatment group was more significant than that of the control group.Conclusion: The combination of traditional Chinese and Western medicine can improve the symptoms of patients, achieve good clinical efficacy, and have certain anti-oxidative stress effects, which is worthy of clinical promotion or further research.

Research Progress of Gualou Xiebai in the Treatment of Coronary Heart Disease

Gualou Xiebai is a basic prescription for the treatment of angina pectoris in Synopsis of the Golden Chamber.This article is a summary of the theoretical research and clinical application of Gualou Xiebai,in hope to promote the use of Gualou Xiebai in clinical practice.

"External main and internal auxiliary" treatment on refractory radiation proctitis

Radiotherapy is an essential method in the comprehensive treatment of malignant tumors.However,radiation proctitis(RP)is a common complication of pelvic tumors after radiotherapy.Due to RP's various etiology and complex pathogenesis,it is currently no standard for traditional Chinese medicine(TCM)treatment.Professor Yuan-hong Zhao believes that refractory RP,which is named chronic hemorrhagic radiation proctitis(CHRP),should be classified as"Intestinal Wind Bleeding"(Bleeding like a note before defecation,bright red blood,no swelling and pain in the anus)and"Intestinal Afflux"(Refers to the symptoms of pus and blood in the lower mucus,similar to ulcerative colitis,peptic ulcer and other diseases in modern medicine.)in TCM.The critical pathogenesis of CHRP lies in local stasis and collaterals injury of intestinal collaterals.In general,it is a syndrome of excess and scarcity.External treatment with TCM is the preferred treatment strategy for CHRP,and the primary way is to disperse blood stasis and detoxify and nourish the intestinal collaterals.

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).

Plasma metabolic biomarkers for syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis

OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome. METHODS： The plasma metabolite profiles of 31 patients with the syndrome of phlegm and blood stasis in hyperlipidemia and As, 6 patients with syn- dromes without phlegm and blood stasis, and 10 healthy subjects were analyzed by gas chromatog- raphy-mass spectrometry （GC-MS）. Partial least squares-discriminant analyses （PLS-DA） were used to carry out the pattern-recognition analyses of the data. The plasma metabolic biomarkers of patients were obtained by variable importance plot value （VlP value） and Student＇s t-test. The structures ofbiomarkers were defined by the National Institute of Standards and Technology （NIST） database. RESULTS： PLS-DA score plots of plasma metabo- Iomes did not show overlap between the phlegm-blood stasis syndrome group and syn- dromes without phlegm and blood stasis group, whereas significant differences in the concentra- tions in the plasma of 5 metabolites were found （P〈 0.05）. They were identified as urine, isoleucine, gluc- uronic acid, palmitic acid and glycerol by searching in NIST database. The concentrations of four metab- olites in the plasma of patients with syndrome of phlegm and blood stasis were higher than those with syndromes without phlegm and blood stasis, whereas the glycerol concentration was lower. CONCLUSION： Compared with patients with syn- dromes without phlegm and blood stasis, five me- tabolites showed abnormal levels in patients with the syndrome of phlegm and blood stasis. These metabolites could be diagnostic and prognostic biomarkers.

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.

Effect of Traditional Chinese Medicine combined with Western Medicine on blood lipid levels and inflammatory factors in patients with angina pectoris in coronary heart disease identified as intermingled phlegm and blood stasis syndrome:a network Meta-anal

OBJECTIVE:To evaluate the clinical efficacy of Traditional Chinese Medicine prescriptions for resolving phlegm in the treatment of angina pectoris of phlegmstasis coronary heart disease by a network Meta-analysis.METHODS:Randomized controlled trials(RCTs)on clinical efficacy of CHD angina pectoris with interaction of phlegm and blood stasis were searched in PubMed,Springer,the Cochrane Library and Chinese-language databases China National Knowledge Infrastructure,China Science and Technology Journal Database,and Wanfang Data from their inception to December 2021.Literature was screened and literature bias risk was assessed by RevMan5.4 software.The overall response rate,the duration of angina attack,the levels of serum lipids such as total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C),and expression of hypersensitive C-reactive protein(hs-CRP)were selected as outcome indicators for network Meta-analysis and mapped using Stata15.1 software.RESULTS:Totally,26 RCTs were included,involving 2098 participants.There were 6 TCM formulas with the effects of dispelling phlegm and removing blood stasis.Taking conventional Western Medicine as the common intervention measures,the results showed that the overall response improvement rate from high to low was displayed as modified Xiaoxianxiong decoction(小陷胸汤,MXD),Danlou tablet(丹蒌片,DT),modified Gualou Xiebai Banxia decoction(瓜蒌薤白半夏汤,MGXBD),modified Wendan decoction(温胆汤,MWD),modified Zhishi Xiebai Guizhi decoction(枳实薤白桂枝汤,MZXGD),and modified Erchen decoction(二陈汤,MED).The sequence of angina attack duration improvement from high to low was MZXGD,MGXBD,DT,MWD,MXD.The sequence of TC improvement from high to low was MZXGD,MED,DT,and MGXBD.Sequence of improving TG from high to low was MED,MZXGD,MGXBD,and DT.For LDL-C improvement,the effect from good to poor was MZXGD,MGXBD,DT,and MED.With regard to HDL-C improvement,the effect was ranked as MED,MZXGD,MGXBD,and DT from good to poor.hs-CRP expression from high to low was MZXGD,MXD,MED,MWD,and MGXBD.CONCLUSION:TCM formula with the effects of dispelling phlegm and removing blood stasis combined with conventional Western Medicine has obvious advantages in treating CHD angina pectoris with interaction of phlegm and blood stasis.MZXGD has great potential in increasing the overall response rate,reducing Duration of angina attack improving blood lipids,and reducing inflammatory factors.However,due to the limitations of extant studies,the conclusions of this study need to be confirmed by numerous reasonably-designed RCTs.

The Proteomic Research of the Cure of Experimental Diabetes Deafness by Granules of Eliminating Phlegm and Removing Blood Stasis

Objective: Observing the expression changes of serum proteome in model rats after intervention of the Granules of Eliminating Phlegm and Removing Blood Stasis (豁痰祛瘀颗粒 also known as GEPRB), screening out and identifying the differentially expressed proteins by mass spectrometry and bioinformatics analysis, discussing the molecular mechanism of control the Diabetes deafness by GEPRB. Methods: By use of proteomics technology, the serum protein serum proteome of the control group, model control group, Duxil and each observation group were observed for 2-DE gel pattern matching, and the difference in the relative content of 2 times was chosen for the differentially expressed proteins. Identification of differentially expressed proteins by MALDI-TOF MS/MS, the authors further analysis the phosphorylation, subcellular localization, interaction, direct regulation, and transmembrane of the differences proteins by the way of bioinformatics analysis. Sixty SPF level SD rats elected in diabetic rats model group (abbreviated as DM group) were be randomly divided into 5 groups based on random number sheet, namely model control group, positive drug control group (Du-ke-xi group) and Mai-tong-fang high, medium and low dose group respectively. In addition, set of normal control group. 10 rats in each group. Results: By Coomassie brilliant blue staining, identified 51 differential protein spots dug from 2-D gel by mass spectrometry, successfully identified 13 non-redundant proteins. Most of the identified proteins were secreted protein and belong to different protein families. There were about 12 proteins have the transmembrane region from the authors’ result, ten of them were plasma membrane proteins. Conclusion: It’s suggesting that 13 differential proteins is most likely the protein response to GEPRB in vivo, these proteins may play key role for the treatment of GEPRB to Diabetes deafness. The two highly differentially expressed proteins Apolipoprotein E (apoE) and C3 may be a potential drug target of GEPRB.

基于UPLC/Q-TOF-MS研究代谢综合征痰瘀互结证的物质基础

目的:采用基于超高效液相色谱与串联四级杆飞行时间质谱仪(UPLC/Q-TOF-MS)联用的代谢组学技术,研究代谢综合征痰瘀互结证动物模型血清中小分子代谢物的变化。方法:模型组大鼠复制成痰瘀互结证代谢综合征,运用UPLC/Q-TOF-MS技术检测空白对照组和模型组血清样本中的小分子代谢产物,对所得到的代谢指纹图谱进行判别分析,找出具有差异的特征代谢物并追溯其来源。结果:鉴定出的潜在生物标志物主要有溶血磷脂酰胆碱、苯丙氨酸、酪氨酸、十四烷酸、硬脂酸、D-葡糖酸、前列腺素B1等内源性代谢物。结论:痰瘀互结证代谢综合征的发生与糖类、脂类、氨基酸代谢紊乱有关,这些体内的小分子化合物可能是痰瘀互结证代谢综合征中医证候的物质基础。

基于UPLC-Q/TOF-MS的痰瘀互结型冠心病患者尿液脂质组学研究

目的开展人尿液脂质组学研究,以期发现痰瘀互结型冠心病患者的脂质生物标志物。方法采集辨证为痰瘀互结型冠心病患者的尿液,同时采集同年龄段健康志愿者尿液,经真空冷冻干燥后采用超高效液相色谱四级杆飞行时间质谱联用仪(UPLC-Q/TOF-MS)进行脂质组学研究,建立正交偏最小二乘判别分析(OPLS-DA)的脂质组学模型,多元统计发现差异脂质代谢物,采用受试者操作特征曲线评价差异脂质代谢物区分痰瘀互结型冠心病患者与健康志愿者的诊断能力。结果健康志愿者与痰瘀互结型冠心病患者尿液脂质组学特征存在显著差异,OPLS-DA模型可有效区分两组样本,发现并鉴别了尿液中13种差异脂质代谢物。结论脂质组学是有效区分健康志愿者和痰瘀互结证患者的有效方法,差异脂质代谢物的发现有助于痰瘀互结型冠心病患者的辨证治疗。

Pathological Mechanism of “Phlegm, Blood stasis, Toxin ”in a Rabbit Model of Carotid Atherosclerosis Based on Gut Microbiota-host Metabolism Interactions

Background:In Traditional Chinese Medicine(TCM)theory,"phlegm,blood stasis and toxin"are the pathogenesis of carotid atherosclerosis(CAS).The rabbit carotid atherosclerosis(CAS),which is induced by high-cholesterol diet combined with carotid artery balloon injury,is a classic model for studying CAS.Many studies indicate that gut microbiota and host metabolic disorders are involved in the pathogenesis of rabbit CAS.However,the TCM pathological features and syndromes of this classic rabbit CAS model have not been reported.Objective:To explore the pathogenesis of the rabbit CAS model and its TCM syndrome types from the perspective of"phlegm,blood stasis,and toxin".Methods:Twelve male New Zealand white rabbits were randomly divided into NC group and CAS group according to their body weight,followed by feeding of basic feed and a 1%high cholesterol diet,respectively.After two weeks,the rabbits in the CAS group underwent common carotid artery(CCA)balloon injury,while the rabbits in the NC group underwent only CCA separation without balloon injury.The two groups received differential feed postoperatively for six more weeks,after which,changes in lipids,hemorheology,inflammation,oxidative stress,and CAS phenotypes were analyzed.In addition,the colon contents and serum were collected for 16S rRNA sequencing and ^(1)H-NMR metabonomic analysis.Results:The CAS rabbits were observed to form noticeable abnormalities in lipid metabolism and blood rhe-ology,a sharp increase in oxidative stress levels,excessive release of inflammatory factors and apparent CAS plaque formation.Furthermore,10 specific gut microbiota(such as Akkermansia muciniphila,Barnesiellaceae and Faecalibacterium)and 14 characteristic metabolites(such as trimethylamine oxide,acetic acid and L-carnitine)were identified in the CAS rabbits,which were significantly related to the CAS phenotypes.The pathway func-tion analysis showed that the gut microbiota and its metabolites mainly affected cholesterol metabolism,energy metabolism,inflammation and oxidative stress.Conclusion:The rabbit CAS model conforms to the“phlegm,blood stasis and toxin damage”theory.The gut microbiota and host metabolic disorders of the CAS rabbits interact and promote internal and external toxins,aggravating the progression of CAS.Our study provided experimental evidence for the application of this model in the TCM-based research of CAS.