The Astragalus Components Of The Energy Metabolism Of Hypertrophied Myocardium Of Rats And Mechanism, And

The heart is a high level energy consuming organ that needs sustained energy supply. The energy metabolism imbalance will cause a series of physiological and pathological changes in morphology, some previous research reported that The energy metabolism dysfunction has been in progressing from the start of the compensatory hypertrophic cardiomyopathy to the heart failure stage, which is the crucial factor. Former study based on the TCM theory showed that The deficiency of heart Qi has emerged before the heart failure occurred and through the entire progress from the beginning of the compensatory hypertrophic cardiomyopathy to the heart failure. The deficiency of Yang and blood stasis, edema which caused by the deficiency of heart Qi as the important syndromes demonstrate the deterioration of heart function. The results based on the TCM theory is similar to the western medicine study. Also Previous study showed that heart Qi and low cardiac function is closely related to Previous study showed that heart Qi, Dangsen and Radix Astragali is effective to heart failure , myocardial energy metabolism can be improved by Radix Astragali with the mechanism of protecting the mitochondrial structure and enhance bio-oxidation related to the activity of a variety of enzymes as well as reducing the depletion of LDH. in hypoxia-ischemia, reperfusion injury and virus damage Myocardial cells.This research is based on sorting out and analyzing a great deal reference data, on the cellular and molecule levels, prove"The deficiency of Qi is the foundation of the heart failure"theory and discuss the protecting mechanism of Radix Astragali preventing and treating the heart failure. At the same time we try to find out the key factors of Radix Astragali accommodating energy metabolism, by the means of research of cardiac myocyte energy metabolism .The experiment part of this research includes two segments. To find out if the Radix Astragali intervene hypertrophy myocardial mitochondrial activity. in the fundamental segment. The core purpose of this experiment is in the second segment , probing into the effect and the key point of Radix Astragali accommodating energy metabolism.Methods1 The first segmentsThe cultured neonatal rat cardiomyocytes were divided into several groups: control group (Control), hypertrophy group (M), Radix Astragali saponins group(AS) and Astragali polysaccharides group (APS). By means of MTT colorimetric method, firstly, observations are going to be carried out in 48 hours ,in order to find out the effect of angiotensin II and various concentration Radix Astragali saponins or Astragali polysaccharides on mitochondrial fumaric redutase activity, while the final target is to select the most suitable concentration of Radix Astragali saponins and Astragali polysaccharides. Secondly, to observe the curve of their effect on mitochondrial fumaric redutase activity in 12 hour,24 hour, 48 hour, 72 hour and 96 hour, as well as to find out the suitable time to observe the curve.2 The second segments The cultured neonatal rat cardiomyocytes were divided into 6 groups: control group (Control), hypertrophy group (M), Losartan group (L), Radix Astragali saponins group(AS) , Astragali polysaccharides group (APS) and Radix Astragali saponins and polysaccharides(AS+ APS). In 24 hour and 48 hour , through the cultured neonatal myocyte hypetrophy induced by AngⅡ, analyze the effects of angiotensin II(Ang II) , Radix Astragali saponins and polysaccharides on ATP content by the means of HPLC, on ATP synthetase (ATPase) activity by the means of measuring Pi through restraining Oligomycin , on total creatine kinase (CK) activity by means of biochemistry method and on creatine kinase isoenzymes which were separated using the Rapid Electrophoresis System . By use of RT-PCR, analyze the influence on ATPase F1 catalytic partβpolypeptide (F1-ATPaseβ), B-CK, M-CK, mito-CK mRNA gene expression.Results1 The most suitable concentration of Radix Astragali saponins and Astragali polysaccharides both was 10-2 g/L. The OD of formazan had no changes by Ang II at 12 hour, was increased significantly at 24 hour, was decreased since 48th hours, more significantly at 72 hour, was still decreased, but the difference was not notable, at 96 hour. After the intervening of Radix Astragali, the OD had no changes by II at 12 hour and was increased significantly at 24 hour, at 48 hour and 72 hour the OD stayed the normal level.2 F1-ATPaseβ's expression was increased obviously and ATP content had no notable changes by Ang II at 24 hour. At 48 hour, F1-ATPaseβ's expression was decreased and ATP content was increased. Neither at 24 hour nor at 48 hour, ATPase activity changed. After the intervening of Radix Astragali, F1-ATPaseβ's expression was increased and ATP content had no notable changes at 24 hour , while F1-ATPaseβ's expression was normal and ATP content was increased higher than control group and lower than M group.3 The expression of CK-B subunits was increased significantly while the expression of CK-M subunits was decreased and the distribution of CK-BB was increased while CK-MM was decreased by AngⅡsince the 24th hours, thus the total CK activity was decreased. At 48th hours, the expression and distribution still stay the same level. The expression of mi-CK subunits had no changed ,either at 24 hour or at 48 hour. In the analyse of CK isoenzymes distribution, CK-MB still stayed the same level and mi-CK can not be separated. After the intervening of Radix Astragali, the phenomenon was alike with it by only AngⅡat 24 hour. At 48 hour, the gene expression, the distribution and the total activity all stayed at the normal level.ConclusionAngⅡcan induce the changes of mitochondrial fumaric redutase activity and induce the changes of ATPase and iso-CK mRNA gene expression , as well as the changes of iso-CK activity and ATP content. It is said that AngⅡcan induce the changes of myocardial energy metabolism substance and correlated enzymes which result in myocardial energy metabolism dysfunction . Radix Astragali can partially prevent these changes. It is accorded with the switch from compensation to decompensation in congestive heart failure in the process of energy metabolism transformation in the cultured neonatal myocyte hypetrophy induced by AngⅡ, also accorded with the symptom of The deficiency of heart Qi. Radix Astragali can prevent and treat the heart failure through enriching heart Qi and removing the blood stasis and diuresis, which was the result of accommodating energy metabolism. One conceivable mechanism is that Radix Astragali prevented the energy metabolism dysfunction induced by AngⅡ. Possibly, the key point is the effect of Radix Astragali on the correlative enzymes gene expression with energy metabolism.