| BackgroundChronic heart failure (CHF) is a common condition in critically illness, and currently it is a major subject in world medical research. Epidemiological survey show that the prevalence of CHF worldwide is increasing, there are 2 tolO million CHF patients out of 500 million people in Europe at least,and about 5 million patients in the United States. The new heart failure patients diagnosed are more than 550 thousond each year.In China, heart failure incidence rate was 0.9%, according to the ratio, of adults aged 35 to 74 at present are still about more than 4 million patients with heart failure, and the upward trend is going on.The CHF Has become the most common clinical disease,coasting more than any other diseases. Therefore the prevention and treatment of CHF is very significant.With understanding the CHF occurring mechanism and studying the relevant reports and literatures during recent years, an undeniable fact is that, despite modern therapy of heart failure, but failed to reduce mortality. Western medicine's side effects, such as antiarrhythmic drugs can cause arrhythmia, digitalis preparations are easy to accumulating poisoning, some drugs as treatment of heart failure such as phosphodiesterase inhibitors, calcium channel blockers and something like those may actually be harmful in heart failure.Chinese medicine as a treatment of CHF has achieved outstanding results in improving heart function, relieving symptoms and improving quality of life, especially with the emergence of new dosage forms of traditional Chinese medicine,the route administratio has been reformed, the treatment of heart failure has been enriched and efficacy has been improved. From the current view, there are few side effects but the advantages of lasting effect. The study of mechanism for Chinese medicine treatment of chronic heart failure has made some progress. With modern experimental methods, many scholars has studied that Chinises medicine therapy can improve cardiac function, hemodynamics, neuroendocrine and biochemical parameters in the system. So they reveals the mechanism for TCM on chronic heart failure to some extent.Acorrding to the mechanism of CHF, Nuanxin capsule is painstakingly developed by Professor Deng Tie-tao, the clinical studies suggest that Nuanxin capsule can significantly improve left ventricular function inpatients with heart failure, increase the 6 minutes walking distance, reduce the rehospitalization rates and improve survival. Besides, Nuanxin capsule can also increase cardiac output in patients with CHF, and enhance cardiacpump function. Based on the above, the intervention of Nuanxin capsule has good results in CHF. However, the mechanism is unclear, experimental studies should be strengthened in order to bright it light. We initially assume that the prevention mechanism of Nuanxin capsule may improve hemodynamics, regulate neuroendocrine and something like those, thus preventing and delaying the ventricular remodeling in order to reduce recurrence of heart failure, delay the course of heart failure and prolong survivalpurposes.Therefore, firstly, to provide the experimental and theoretical basis, this study based on the effective clinical efficacy of Nuanxin capsule, and then tap the specific mechanism of action, making indepth research around the left ventricular remodeling and related issues, prevention and treatment of chronic heart failure. Secondly, to enrich possible mechanism of Nuanxin capsule, which will be preparatory work to make it a new drug as an effective treatment for CHF.Purpose1.To observe the clinical efficacy of Nuanxin capsule on patients with CHF;2. To study affect of Nuanxin capsule on the ventricular remodeling from some aspects by modeling rats into heart failure. Contents and methods1.Clinical research1.140 patients with chronic heart failure were randomly divided into control group and treatment group,20 patients in each group,control group received routine anti-heart failure drugs;treatment group were added Nuanxin capsule based on anti-heart failure drugs.Treatment for 4 weeks.1.2 Laboratory tests blood routine, urine routine, stool routine, liver and kidney function as a security index to determine whether warm capsule toxic side effects.1.3 TCM syndrome score and cardiac function were observed before and after treatment.1.4 Echocardiography indicators were detected before and after treatment.2.Animal experiment2.1 Grouping and modeling:91 SD male rats,13 were randomly selected as the control group, and the remaining 78 intraperitoneal injection of doxorubicin modeling of heart failure after 4 weeks were randomly divided into 6 groups (ADR heart failure model group, Nuanxin capsule low, medium and high dose group, Captopril group, Xinbao pill group),13 in each group.2.2 Administration methods:Nuanxin low, medium and high dose group were given 0.45g/kg/d,0.9g/kg/d and 1.8g/kg/d, Captopril group was given 6.75mg/kg/d, Xinbao pill group 194.4mg/kg/d, the control group and ADR heart failure model group were given same volume water for six weeks.2.3 After six weeks, to detect indicators of hemodynamics, AngⅡ, ALD, Ca2+-ATPase and matrix metalloproteinase(MMPs)activity, and observe myocardial pathological ultrastructure in heart failure rats.Results1. Clinical research1.1 Comparison of before and after treatment, SV, ST, CO, CI were significantly different in the treatment group(P＜0.05) and control group(P＜0.05). After treatment, comparison of the treatment group and control group, SV, SI, CO, CI were significantly different (P＜0.05). After treatment, SV, SI, CO, CI were increased significantly in both groups (P＜0.05).1.2 The improvement of cardiac function:After treatment, the total effective rate was 96% in the treatment group, the total effective rate was 80% in the control group, and the treatment group was significantly higher than control group. Comparison of the treatment group and control group, the effects of NYHA class were significantly different (P＜0.05).1.3 TCM syndromes:After treatment, the total effective rate was 92% in the treatment group, the total effective rate was 80% in the control group, and the treatment group was significantly higher than control group. The Ridit analysis showed that the comparison of TCM syndromes between the two groups was significantly different(P＜0.05), and the treatment group was better than control group in improving the efficacy of TCM syndrome.1.4 Statistical analysis showed that the comparison was significantly different(P＜0.05)in improving asthma, drowsiness, fatigue, poor appetite, leg swelling and other symptoms between the two groups, and the efficacy of the treatment group was better than control group;There was no significant difference in the comparison of other symptoms between the two groups (P>0.05).1.5 Safety monitoring results indicated that there was no worsing comparing with before treatment, and Nuanxin capsule has good tolerance with no significant or serious adverse reactions.2. Animal experiment2.1 Hemodynamics resultsCompared with the ADR group, there were increasing onSAP, DAP, LVSP,±dp/dtmaxin every Nuanxin capsule groups, especially in medium and high-dose groups (P＜0.05 or P＜0.01), while the same role in the captopril and Xinbao pill groups (P＜0.05 or P＜0.01).2.2 Determination of heart, lung and liver weight indexCompared with the ADR group, there were reducing on heart, lung and liver weight index in every treatment groups, especially on heart weight index (P＜0.05 or P＜0.01), and there were reducing on liver weight index in Nuanxin capsule medium-dose,captopril and Xinbao pill groups(P＜0.05).2.3 Morphological observation of heart, lung and liver2.3.1 Light microscopyCompared with the ADR group, there were improvement on myocardial morphology in every treatment groups, especially there was in Nuanxin capsule high-dose group.2.3.2 Electron microscopyCompared with the ADR group, there were significant improvement on myocardial morphology in Nuanxin capsule high-dose, captopril and Xinbao pill groups.2.4 SERCA2a activity and plasma AngⅡ,ALD levelsCompared with ADR group,there were significantly increasing on SERCA2a activity in Nuanxin capsule medium and high-dose groups, also the captopril and Xinbao pill groups(P＜0.05 or P＜0.01), plasma AngⅡ,ALD levels lowered significantly(P＜0.05 or P＜0.01).2.5 Myocardial MMP-1, MMP-9, TIMP-1 gene expressionCompared with ADR group, there were improvement on MMP-1 and TIMP-1 in every Nuanxin capsule groups, but no significant difference(P>0.05),a distinct role on MMP-9, especially in medium and high-dose groups (P＜0.05), the captopril and Xinbao pill groups also had significantly effects on MMP-9(P＜0.05).Conclusions1. Nuanxin capsule for patients with CHF has the exact effect without any toxicity and side effects, Which is effective and safe traditional Chinese medicine for CHF.2. On the basis of effective clinical studies, using ADR by intraperitoneal injection,to replicate CHF rat model successfully,and investigate the mechanism of Nuanxin capsule on treating CHF:2.1 Nuanxin capsule can improve the levels of±dp/dtmax, LVSP and lower LVEDP, enhancing systolic and diastolic performance, reducing heart rate, thus effectively improving thehemodynamics.2.2 Nuanxin capsule can significantly reduce the plasma AngII,ALD in CHF rats, blocking the RAAS activation, regulating neuroendocrine levels and preventing myocardial remodeling.2.3 Nuanxin capsule can enhance myocardial SERCA2a activity, and improve the energy supply, in order to increase Ca2+-uptaking capacity, and improve cardiac diastolic and systolic function.2.4 Nuanxin capsule can improve the myocardial expression of TIMP-1 protein, while reducing the MMP-1, MMP-9 expression,thus effectively preventing the degradation of collagen and matrix remodeling, preventing left ventricular expansion, delaying process of CHF.3. Through this experiment we found that Nuanxin capsule could inhibit cardiac remodeling with multi-gene, multi-system, multi-target, multi-faceted comprehensive regulati on, and which is one of effective methods in preventing and treating CHF. |
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