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.

Energy Metabolism Disorder and Myocardial Injury in Chronic Myocardial Ischemia with Qi Deficiency and Blood Stasis Syndrome Based on 2-DE Proteomics

Objective： To inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis （2-DE） map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome. Methods： Ameroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF-MS） were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome. Results： The preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDI- TOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 （NAD＋） alpha, NADH dehydrogenase （NAD） Fe-S protein 1, chain A （crystal structure of aidose reductase by binding domain reveals a new Nadph）, heat shock protein 27 （HSP27）, oxidoreductase （NAD-binding protein）, antioxidant protein isoform, cardiac troponin T （cTnT）, myosin （myosin light polypeptide）, cardiac alpha tropomyosin, apolipoprotein A- I and albumin. Conclusion： Down-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker（s） for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine

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.

Serum Low-Density Lipoprotein and Heart Rate Related to the Effectiveness in the Treatment of Angina Pectoris with Two Similar Chinese Medicine Herbal Formulae

Objective： To explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule （通心络胶囊） and Kangxin Capsule （康欣胶囊） targeting on qi deficiency and blood stasis pattern in Chinese medicine （CM） in the treatment of angina pectoris. Methods： The data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1：1 ratio to Tongxinluo Capsule group （119 cases） and Kangxin Capsule group （120 cases）. Angina effectiveness and electrocardiogram （ECG） improvement were selected as the therapeutic outcomes. Results： After a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively （P〈0.05）. Serum low-density lipoprotein （LDL） level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate ≤80 beats/min. Conclusion： LDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.