| (?)Part one Literature ResearchThis research based on referring to domestic and international literature and observing the current research situation of CHF, and mastered the cognition of etiology, treatment based on syndrome differentiation and the clinical experience of modern traditional Chinese physician. We also summarized’the research method and achievements of TCM and western medicine in treating CHF for the past few years and provided solid theory support for clinical and experimental study.Part two Clinical Research1. ObjectiveTo objectively evaluate clinical safety and effect on treatment of CHF using wenyangzhenshuai granule and to provide the theoretical basis for wenyangzhenshuai granule being approved by the State for production and sale.2. MethodTaking the currently accepted treatment of CHF as a control, we carried out a prospective, randomized and controlled clinical study. Cases included in this study were randomly divided into control group and treatment group. Cases of control group received basic therapy and cases of treatment group received basic therapy plus wenyangzhenshuai granule, half of granule each time,2times a day and for4weeks.We observed the changes in ultrasound cardiogram, serum cytokines, TCM syndroms, heart failure syndromes and Minnesota Satisfaction Questionnaire Scales of patients with heart failure before and after treatment.3. Result(1) comparison of curative effect on TCM syndromes and heart failure syndromes, there was a statistically significant difference in efficacy between the two groups (P<0.05).(2) comparison of scores on TCM syndromes and heart failure syndromes showed that after treatment, changes of two groups had a statistically significant comparing with before treatment (P<0.05).Changes of treatment group decreased more significantly than that of control group(P<0.05).(3) comparison of scores of Minnesota Satisfaction Questionnaire Scale:after treatment, scores of two groups had a significantly lower, and comparing with before treatment, the difference was statistically significant(P<0.05).Scores of treatment group decreased more significantly than that of control group(P<0.05).(4) comparison of curative effect on ultrasound cardiogram showed that after treatment, changes of two groups had a statistically significant comparing with before treatment (P<0.05).Changes of treatment group increased more significantly than that of control group(P<0.05).(5) comparison of serum NT-proBNP,TNF-a,IL-1and IL-6:after treatment, changes of two groups had a significantly lower, and comparing with before treatment, the difference was statistically significant(P<0.05).Changes of treatment group decreased more significantly than that of control group(P<0.05).4. Conclusion(1) wenyangzhenshuai granule can further relieve clinical symptoms of patients with CHF based on the basic treatment of western medicine.(2) wenyangzhenshuai granule can improve the life quality of patients with CHF based on the basic treatment of western medicine.(3) wenyangzhenshuai granule can improve the heart function and reduce serum NT-proBNP of patients with CHF based on the basic treatment of western medicine.(4) wenyangzhenshuai granule can reduce serum cytokines of patients with CHF based on the basic treatment of western medicine.(5) wenyangzhenshuai granule possess good security.Part three Experimental Research1. ObjectiveObserved the protective effect of wenyangzhenshuai granule for heart structure and function of rabbit model with CHF and it’s influence on serum NT-proBNP, serum cytokines and extracellular signal-regulated kinase1/2, and evaluate the efficacy in delaying ventricular remodeling and inhibiting myocardial apoptosis by using wenyangzhenshuai granule.2. MethodMaking adriamycin-induced chronic heart failure animal model. The experimental animals were divided into control group, experimental control group, captopril group, wenyangzhenshuai low, medium and high dose groups. At5weeks after’ the first injection of adriamycin, rabbits in wenyangzhenshuai low, medium and high dose groups were perused orally with wenyangzhenshuai granules.5experimental rabbits in each group were sacrificed respectively at the end of the4th and8th week to investigate the effects of wenyangzhenshuai granule on ultrasound cardiogram, serum NT-proBNP, serum cytokines, extracellular signal-regulated kinase1/2, myocardial apoptosis and myocardial ultrastructure.3. Result(1) the LVEF, LVFS and E/A of experimental groups had a statistically significant difference to the control group at the end of4th weeks(P<0.05), the level of LVEF, LVFS and E/A decreased at the end of8th weeks, which had a statistically significant difference to the control group(P<0.05), the other experimental groups decreased slower than experimental control groups (P<0.05). (2) comparison of serum NT-proBNP and cytokines in each groups, the experimental groups were higher than the control group at the end of4th weeks(P<0.05), the level of serum NT-proBNP and cytokines increased at the end of8th weeks, the wenyangzhenshuai granule medium and high dose groups increased slower than other groups (P<0.05).(3) the myocardial ERK1/2and ERK1/2mRNA levels in each group at the end of4th and8th weeks were not significantly different than those in the other groups at the same time (P>0.05). The myocardial P-ERK1/2levels in the model control group and wenyangzhenshuai three dose groups were higher than that in the normal control group at the end of4th weeks (P<0.05). With the modeling time prolonged, P-ERK1/2expression in the model control group showed an increasing trend. At the end of8th week, the myocardial P-ERK1/2expressions in the wenyangzhenshuai three dose groups at4weeks after treatment were increased to some extent compared to previous levels, but were lower than that in the experimental control group (P <0.05), of which, the myocardial P-ERK1/2level in wenyangzhenshuai high dose and captopril groups was increased at the slowest pace compare to the wenyangzhenshuai low and medium groups (P<0.05).(4) comparison of apoptosis index in each groups, the experimental groups were higher than the control group at the end of4th weeks(P<0.05), the level increased at the end of8th weeks, the wenyangzhenshuai granule medium and high dose groups increased slower than other groups (P<0.05).(5) the LVDd and LVDs levels in each group at the end of4th weeks were not significantly different than those in the other groups at the same time (P>0.05). The IVS and LVPW levels of experimental groups had a statistically significant difference to the control group at the end of4th weeks(P<0.05). The trend of cardiac enlargement in the experimental groups decreased at the end of8th weeks compare to the experimental control group(P<0.05), which the wenyangzhenshuai high dose group was increased at the slowest pace(P<0.05).(6) results of optical microscopy:the myocardial structure of experimental control group and drug intervention groups were irregular, which had muscle fiber fracture and myocardial cell edema or inflammatory cells infiltration. The myocardial pathological changes in wenyangzhenshuai high dose group was better compare to the other groups. Results of electron microscopy:In the experimental control group and drug intervention groups, the muscle fiber were necrosis or atrophy, mitochondria edema and vacuolization, filament structure is also not clear and with inflammatory cells infiltration. The myocardial pathological changes in wenyangzhenshuai high and medium dose groups were better than the other groups.4. Conclusion(1) wenyangzhenshuai granule can effectively improve the heart function in chronic heart failure model in rabbits and decrease the serum NT-proBNP level.(2) wenyangzhenshuai granule can effectively reduce the serum cytokines level in chronic heart failure rabbit model.(3) wenyangzhenshuai granule can inhibit myocardial P-ERK1/2expressions in rabbit models of chronic heart failures, but had no significant impact on myocardial ERK1/2and ERKl/2mRNA levels.(4) wenyangzhenshuai granule can effectively reduce the apoptosis index level in chronic heart failure rabbit model.(5) wenyangzhenshuai granule can delay the cardiac structure changes in chronic heart failure rabbit model and improve the ultrastructure of myocardial tissue, it can also partly inhibit ventricular remodeling. |
PDF Full Text Request