| Congestive heart failure (CHF) is a common disease, and has become one of the most important public sanitary problems. CHF is the end-stage of various heart diseases. Operation and invention treatment are not widely used, and the major one is still drug treatment. Although the application of ACEI andβ-blocker could improve the life quality and exercise tolerance of patients with heart failure, the prognosis is so poor that the mortality is as high as 10 to 50 percent.The treatment with traditional Chinese medicine for congestive heart failure is a major feature of traditional Chinese medicine. Clinic reports are not unusual, but systemic reports on both clinic and laboratory are not yet common. The Study that is associated with the treatment with traditional Chinese medicine for congestive heart failure is lack of depth. Jian Xin Soup has been used in clinic and be testified effectively to treat heart failure. However, the exact mechanism of anti-heart failure treatment is not yet known and need to be explored further. The possible mechanism of Jian Xin Soup curing congestive heart failure from both clinical and experimental sides will be explored in further study. Part 1: Clinical ResearchObjective: To investigate the effect and safety of Jian Xin Soup on CHF and to study its probable mechanism.Methods: 50 Patients with CHF and NYHA grade II-III were studied, and randomly divided into the treatment group (n=25) and control group (n=25). The control group was treated with conventional western medicine, while the treatment group was treated with Jian Xin Soup twice a day for 6 weeks as well as western medicine. Side-effects and heart function were recorded during drug administration. 6 minute walk test (6MWT) and Minnesota living with heart failure questionnaire (MLHFQ) were also used to estimate exercise performance and life quality. The level of plasma NT-proBNP and Copeptin was investigated by ELISA assay.Results: 1. The total effective rate in treatment group was 92%, while in control group was 80%, there was significant difference between the two groups (P<0.05) .2. Lee's marks of CHF and NYHA classification was decreased significantly in both groups after treatment (P<0.05) ,and with even better decrease in treatment group than that in control group (P<0.05) .3. The LVEF, LVESV and FS was improved significantly in both groups after treatment (P< 0.05),but the improvement in treatment group was more significant than that in control group (P<0.05) . After treatment, there was significant difference in treatment group with LVEDV than that before treatment (P<0.05) , but with no significant difference in control group (P>0.05) .4. After treatment, the distance of 6MWT was increased signifieantly in both groups (P<0.05) ,and with even better increase in treatment group than that in control group (P<0.05) .5. After treatment, the concentration of NT-proBNP and Copeptin was decreased significantly in both groups (P<0.05) ,and with even better decrease in treatment group than that in control group (P<0.05) .6. After treatment, the marks of MLHFQ was decreased significantly in both groups (P<0.05) ,and with even better decrease in treatment group than that in control group (P<0.05) .7. No side-effects such as the liver and kidney function damage were recorded in both groups.Conclusions: 1. Jian Xin Soup could strengthen the therapeutic effects, improve heart function, enhance exercise performance and life quality, and it has cooperative function with conventional western medicine on CHF treatment.2. Jian Xin Soup could decrease the level of NT-proBNP and Copeptin, and it may suggest that Jian Xin Soup is effective in the treatment of CHF.3. Jian Xin Soup has no side effects, and it is very safe in six weeks. Objective: To investigate the effects of Jian Xin Soup on heart function and left ventricular remodeling in order to find some possible mechanism and provide evidence to clinical application.Methods: 76 model rats with CHF were randomly divided into 4 groups, that is, Jian Xin Soup low dose group, Jian Xin Soup high dose group, HF control group, and Perindopril group, 19 in each group. Another 15 rats are the sham operation group. In Jian Xin Soup low dose group, each rat is fed with 7.65g/kg; in Jian Xin Soup high dose group with Jian Xin Soup 15.30g/kg, and in Perindopril group with Perindopril 0.72mg/kg, Sham operation group and the control group is fed with 1ml/kg water. All rats were fed twice a day for 6 weeks. The measurement included: (1) mortality, body weight, total heart mass indexes(THMI),and left ventricular mass indexes(LVMI) were observed; (2) before and after the treatment, the IVST, LVPWT, LVEDD, FS, LVEF were recorded by Echocardiography; (3) pathologic changes of left ventricular myocardium were viewed with HE staining method; (4) collagen volume fraction (CVF) was done with patho-image analytical system; Expression of collagen type I and III was measured by immuno-hisochemical method, and the ratio of collagen type I and III was calculated; (5) concentration of AngII and ET in left ventricular myocardium was measured by radio-immunity method, the level of plasma NT-proBNP was measured by ELISA assay. The levels of ET and NT-proBNP mRNA in left ventricular myocardium were measured by RT-PCR; (6) the expression of p-ERK1/2 and p38-MAPK in left ventricular myocardium was measured by Western blot.Results: 1. After the medication treatment, the mortality, THMI and LVMI were significantly decreased in those of all treatment groups (P< 0.05) , but there was no obvious difference among the treatment groups (P>0.05) .2. Compared to sham operated group, in HF control group LVEDD was obviously increased and FS LVEF was decreased (P<0.05) ; After treatment, heart function improved compared to that of HF control group(P<0.05) , FS and LVEF were better in Jian Xin Soup high dose group and Perindopril group than those in Jian Xin Soup low dose group.3. After the treatment of Jian Xin Soup, the pathomorphology of myocardium had been improved with dose-dependence, they were better in Jian Xin Soup high dose group and Perindopril group than those in Jian Xin Soup low dose group, but there was no obvious difference between Jian Xin Soup high dose group and Perindopril group.4. After the medication treatment, the levels of type I collagen, ratio of collagen type I and III and CVF were significantly decreased in all treatment groups (P<0.05), lower in Jian Xin Soup high dose group and Perindopril group than that in Jian Xin Soup low dose group.5. After the medication treatment, the level of AngII, ET and NT-proBNP were significantly decreased in all treatment groups (P< 0.05), but the level of AngII was the lowest in Perindopril group compare to that in the other two groups (P<0.05) . The levels of ET and NT-proBNP were lower in Jian Xin Soup high dose group and Perindopril group than those in Jian Xin Soup low dose group, but there was no obvious difference between Jian Xin Soup high dose group and Perindopril group (P>0.05) .6. After the medication treatment, the levels of p-ERK1/2 and p38-MAPK were significantly decreased in all treatment groups (P< 0.05) , but the levels of p-ERK1/2 and p38-MAPK were lower in Jian Xin Soup high dose group and Perindopril group than those in Jian Xin Soup low dose group, but there was no obvious difference between Jian Xin Soup high dose group and Perindopril group (P>0.05) .Conclusions: 1. Jian Xin Soup may be effective in the treatment of CHF through improving the CHF rats' heart function and tissue morphology.2. Jian Xin Soup could decrease the level of type I collagen, ratio of collagen type I and III and CVF, it may regress ventricular remodeling through reversing collagen remodeling.3. Jian Xin Soup could decrease the level of AngII, ET and NT-proBNP, it may regress ventricular remodeling through restraining over-excitation of nerve endocrine system.4. Jian Xin Soup could decrease the level of p-ERK1/2 and p38-MAPK, it may regress ventricular remodeling through regulating the abnormal signal pathway of ERK and p38.5. Jian Xin Soup could improve heart function and regress ventricular remodeling. There was no obvious difference in therapeutic effects between Jian Xin Soup and Perindopril in six weeks.
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