| ObjectiveTo observe Xinyang tablet’s clinical effect on subjects of coronary heart disease chronic heart failure with qi-yang deficiency,blood stasis and water stagnation s yndrome by prospective randomized controlled trial.At the same time,to observe the effect of Xinyang tablets on plasma metabolites of subjects of coronary heart disease chronic heart failure with qi-yang deficiency,blood stasis and water stagnation syndrome,and to find out the possible biomarkers of Xinyang tablets.Methods1.Clinical study: According to the inclusion criteria and exclusion criteria,28 subjects of coronary heart disease chronic heart failure with qi-yang deficiency,blood stasis and water stagnation syndrome were randomly divided into two groups: CCHF-T group(treated by Xinyang tablets and conventional western medicines)and CCHF-C group(treated by conventional western medicines).The course of treatment was four weeks.The levels of plasma N-terminal pro-brain natriuretic peptide(NT-pro BNP),6min walking distance(6MWD),classification of cardiac function,clinical symptom score of TCM and Minnesota Heart Failure Quality of life questionnaire score were measured before and after treatment.SPSS 26.0 was used to analyze the data.2.Metabonomics study: Based on subjects of coronary heart disease chronic heart failure who completed the clinical study above,according to the inclusion criteria and exclusion criteria,20 subjects of coro nary heart disease without heart failure(CHD-C group)and 11 healthy people(H-C group)were included.SPSS 26.0 was used to analyze the baseline data.Blood samples were collected from subjects of coronary heart disease chronic heart failure before and after treatment,CHD-C group and H-C group,respectively.The samples were sent to Beijing N uohe Zhiyuan Technology Co.,Ltd.for LC-MS detection.Quality control(QC)was performed on the test data.Principal component analysis(PC A)and partial least squares discriminant analysis(PLS-DA)were performed on the meta-X.The differential metabolites were screened by referring to the variable importance in the projection(VIP)of the first principal component of the PLS-DA model,fold change(FC),and P-value calculated by t-test.Results1.Clinical study:(1)There were no significant differences in gender,age,course of treatment,left ventricular ejection fraction(LVEF),combined diseases,and plasma NT-pro BNP level,6MWD,classification of cardiac function,clinical symptom score of TCM,and Minnesota Heart Failure Quality of life questionnaire score before treatment between the two groups(P>0.05).(2)Plasma NT-pro BNP level: After treatment,the plasma NT-pro BNP levels of subjects of coronary heart disease chronic heart failure in both groups were significantly lower than those before treatment(P<0.05).However,there was no significant difference between the differences of each group(P>0.05).(3)6MWD: After treatment,6MWD of subjects of coronary heart disease chronic heart failure in both groups were significantly lower than those before treatment(P<0.05).Nevertheless,there was no significant difference between the difference of each group(P>0.05).(4)Classification of cardiac function: After treatment,there was no significant difference in the curative effect of classification of cardiac function between the two groups of subjects with coronary heart disease chronic heart failure(P>0.05).(5)C linical symptom score of TCM: After treatment,the clinical symptom scores of TCM of subjects with coronary heart disease chronic heart failure in the two groups were significantly reduced(P<0.05).There was a significant difference between the difference of each group(P<0.05).The total effective rate of the CCHF-T group was 90.9%,while that of the CCHF-C group was 76.9%.The total effective rate of CCHF-T was significantly higher than that of CCHF-C(P<0.05).(6)Minnesota Heart Failure Q uality of life questionnaire score: After treatment,the scores of the two groups of subjects with coronary heart disease chronic heart failure were significantly reduced(P<0.05): There was a significant difference between the difference of each group(P<0.05).2.Metabonomics study:(1)There were no significant differences in gender and age among CCHF-T +CCHF-C group,CHD-C group,and H-C group(P>0.05).There was no significant differences in the combined disease status between CCHF-T group and CCHF-C group,and between CCHF-T+CCHF-C group and CHD-C group(P>0.05).(2)Pearson correlation analysis of QC samples showed that the correlation of QC samples was high,PCA of total samples showed that the difference of QC samples was slight.(3)PCA showed that after treatment,the CCHF-T group and CCHF-C group showed a significant separation trend from before treatment and tended to the H-C group.PLS-DA also showed that after treatment,the CCHF-T group and CCHF-C group showed a significant separation trend from before treatment.(4)A total of 140 characteristic differential metabolites of Xinyang tablets intervention and 291 characteristic differential metabolites of chronic heart failure(CHF)were obtained,and 33 characteristic differential metabolites of Xinyang tablets in the treatment of CHF were obtained.The 7 metabolites were down-regulated in subjects with CHF,but upregulated by Xinyang tablets(P<0.05).4-ethoxy-n-[(4-methoxy-n-]Xyphenyl)methylene]-aniline was the only metabolite which was up-regulated in subjects with CHF and upregulated by Xinyang tablets(P<0.01).25 metabolites were up-regulated in subjects with CHF,but down-regulated by Xinyang tablets(P<0.05),among which,13-HPODE,3-[1-(dimethylamino)-1H-pyrrol-2-yl]-2-(2-furylcarbonyl)acrylonitrile,3-[(2-phenyl-1Himidazol-4-yl)methylene]-1,3-dihydro-2H-indol-2-one,N’-(4-methoxy-1,3-benzothiazol-2-yl)-N,N-dimethyliminofor-mamide,Thymopentin,4-(4-hydroxy-3,5-dimethylphenyl)-2-methylphthalazin-1(2H)one,RKK,Cryptotanshinone,Oxohongdenafil,Oxfendazole,Natamycin(11 metabolites)were significantly down regulated by Xinyang tablets(P<0.01).Conclusion1.Xinyang tablets can significantly improve the clinical symptoms and quality of life of patients wih coronary heart disease chronic heart failure.2.Xinyang tablets may treat patients of coronary heart disease chronic heart failure with qi-yang deficiency,blood stasis and water stagnation syndrome by reverse upregulating 7 plasma metabolites such as LPC 20:5,reverse down-regulating 25 plasma metabolites such as 13-HPODE,and up-regulating 4-ethoxy-n-[(4-methoxyphenyl)-methylene] aniline in the same direction. |
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