| Heart failure is one of the most serious killers. In the normal heart, energy metabolism and function are exquisitely matched. Ischemic heart diseases, encompassing and ranging from angina pectoris to acute myocardial infarction, have a major impact on both cardiac energy metabolism and cardiac function. In the stressed heart, metabolic remodeling precedes, and sustains functional and structural remodeling. However, during and after ischemia there are both a decrease in energy production and disturbances in the balance between use of fatty acid and glucose by the heart. It is considered to be an overloading cardiomyopathy due to insufficient energy for a long time.As new insights' are gained into metabolic adaptation and maladaptation of the heart, metabolic modulation may become an effective strategy in the treatment of heart failure. Thus the multitude of targets available to optimize myocardial energy metabolism may significantly increase the armamentarium of therapeutic interventions for preserving cardiac contractile function and limit the untoward effects of ischemic heart disease. Metabolic energy modulation may represent a promising means to improve contractile performance of the heart. There is an urgent clinical need for agents that improve cardiac performance with a favorable safety profile. These current novel approaches to improving cardiac function provide the hope that such agents may soon be available. Herbs of replenishing qi show the role of improvement in cardiac function and myocardial energy metabolism optimize. In TCM pathogenesis, heart failure is asthenia of cardiac qi. It is a combining site to research the problems that mechanism of pathology and physiology on insufficient energy based on the disease-syndrome animal model of heart failure and asthenia of cardiac qi.Objective:To evaluate the metabolic remodeling of myocardial energy in acute myocardial infarction and the role of improvement in cardiac function and myocardial energy metabolism influence shown by herbs to replenish qi in rats.Methods: One hundred and forty Sprague Dawley (SD) rats were randomly divided into seven groups, made rat models of heart failure after myocardial infarction by ligaturing coronary artery. Rats in the sham operation group, model control group and five treatment groups received different drugs in the same three and nine weeks, then scored them by clinical TCM asthenia of cardiac qi syndrome differentiating criteria and heart failure diagnostic criteria quantificational. It was pathological and about TCM syndrome. The indexes were heart function, heart rate, respiratory rate, swimming-exhausted time, etc. Made standard rat model of heart failure and asthenia of cardiac qi, researched its hearts infarction zone by 31P-NMR of ATP & PCr in the same time of different groups, to find the change of heart energy metabolism. On the Myocardial energy metabolism regulation mechanism of the key molecular by means of biochemistry method and on B-CK, M-CK, mi-CK, iso-adenine nucleotide translocator (ANT) mRNA gene expression by using RT-PCR, on protein expression by using western-blot.Results:1. Heart failure and asthenia of cardiac qi(high heart rate, high respiratory rate, short swimming-exhausted time and low heart function, P＜0.05, P＜0.01), were pathological and physiological respectively. They had asthenia of cardiac qi. Herbs of replenishing qi could significantly improve symptoms of rat models on reducing heart rate, extending the swimming time, the systolic blood pressure, left ventricular±dP/dtmax (P＜0.05, P＜0.01), and declining the left ventricular diastolic terminal pressure (P＜0.05), totally improving the heart function of rats with the CHF model.2. The myocardial energy substance ATP and PCr content of CHF rat model was significantly decreased (P＜0.05, P<0.01) by using 31P-NMR. Herbals of replenishing qi could significantly increase the myocardial energy content of the rat model (P<0.05, P＜0.01).3. ANT1, ANT2 and CK-M mRNA gene expression of the CHF rat model were lower, the difference between the model group and control was significant (P＜0.05, P＜0.01), herbs of replenish qi could raise it to the normal level(P＜0.05, P＜0.01). The CK-B mRNA gene expression of the CHF rat model were high(P＜0.01), herbs to replenish qi could reduce it to the normal level(P＜0.05, P＜0.01). The CK-MB, CK-MM, mi-CK protein expression of the CHF rat model were lower, while the difference between the model group and control was not significant, herbs of replenish qi could raise it to the normal level. The CK-BB protein expression of the CHF rat model was high(P＜0.01), herbs of replenish qi could raise it to the normal level(P＜0.05, P＜0.01). Conclusion:Herbs to replenish qi can maintain the stability of the material content of myocardial energy and energy regulation mechanism, thus significantly relieve heart palpitations, fatigue, shortness of breath due to heart qi deficiency and chronic heart failure, and significantly improve the function of systolic and diastolic of the left ventricular. In conclusion, this study highlights that the metabolic remodeling of myocardial energy is an important mechanism of chronic heart failure and heart qi deficiency. |
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