| Chronic heart failure (CHF) is the terminal stage of a variety of cardiovascular diseases. In the 21st century CHF is one of the most common epidemics, which troubled 1/6 adults. Cardiac hypertrophy is a major compensatory mechanism for heart failure and important part of the pathophysiology of heart failure. Once heart failure occurs, the prognosis is extremely poor. The 5-year survival rate of patient whose heart function in NYHA III,Ⅳgrade less than 50%. Although with ACEI andβ-receptor blockers, the treatment has been improved, but the morbidity rate, mortality remains high, the early prevention is the best intervention strategy. Therefore should pay attention to the early pathogenesis of heart failure.Besides the reduction of the number of cardiac myocytes and mechanical incoordination on insynchronization of each parts of ventriculium, the cardinal mechanism of heart failure is the systolic and/or diastolic dysfunction of myocardial myocytes. In normal excitation-contraction coupling (ECC), firstly, small amounts of calcium ions enter the cell through L-type calcium channel during depolarization, then a large of calcium release from sarcoendoplasmic reticulium (SR) by ryanodine receptors. This is called the calcium-induced calcium release. The result is a rapid rise of cytosolic calcium concentration that causes myocardium contraction. Then during repolarization, most of the cytosolic calcium is uptaken into sarcoendoplasmic reticulum by its Ca2+-ATPase (SERCA2) under the regulation of phospholamban. Meanwhile a part of calcium is transported out of the cell through the membranous Na+-Ca2+ exchanger (NCX1) to balance the amounts of calcium that enters through L-type calcium channel. So the concentration of calcium in cytosol decreases and the myocardium relaxes. This change of intracellular calcium ions during excitation-contraction coupling is called calcium transient, and it is the molecular basis of myocardial contraction. A lot of studies indicate that calcium transient is abnormal in chronic heart failure. Compareing to calcium transient of normal myocardium, the ascenting and descenting velocity of calcium transient is slower, and the amplification is smaller in failure myocardial myocytes. These changes of calcium transient, which would give rise to the cardiac dysfunction, are caused by the changes of calcium handling proteins.Sarcoplasmic reticulum calcium transport has become to be considered is one of the most mechanisms during the development of heart failure, and may be the target for intervention in the future. But no corresponding drugs for clinical application. Traditional Chinese medicine has certain advantages in early intervention in heart failure. During the clinical studies, the researcher suggests that deficiency of qi, blood stasis is the cause of heart failure occurred, and a key factor for heart failure. Previous experiments also suggested that traditional Chinese medicine has different regulation for sarcoplasmic reticulum calcium transport. Salvia and Astragali is effective to heart failure which is commonly used drugs, with the exact clinical efficacy. There can impro ve cardiac hypertrophy, but also can delay the progress of heart failure. But so far, have not seen the researches for sarcoplasmic reticulum calcium transport in hypertrophic cardiac. Besides the lack of hypertrophic cardiac myocytes calcium transient effects and sarcoplasmic reticulum calcium transporter protein reported.This research is based on sorting out and analyzing a large of reference data and previous research, in cellular and molecular level, from the cardiac sarcoplasmic reticulum calcium transport mechanism is available to proof the "Salvia and Astragali has benefit for heart failure by improving the cardiac sarcoplasmic reticulum calcium transport and thus prevent the development of cardiac hypertrophy to heart failure "theory and discuses the mechanism of Salvia and Astragali in pharmacology.1. Effects of Salvia and Astragali on the Survival Rate of normal myocardial cells and myocardial hypertrophy cells.MethodsThe cultured of neonatal rat cardiomyocytes were divided into control group (Control, C), hypertrophy group (Model, M), Salvia injection group (DS), Radix Astragali Injection Group (HQ), Salvia and Radix Astragali Injection group (DQ), By means of MTT colorimetric method, observations of angiotensinⅡ(AngⅡ) and different concentrations of Astragali and Salvia Injection on myocardial cell viability, determine the most appropriate Astragali and Salvia Injection concentration.ResultsThe most suitable concentration of Salvia and Astragalus both was 10-6g/L, The OD of formazan had significantly effects at 24th hour, but the drug effects was not strong. The effects was decreased since 48th hour, the treatment group at this time can increase the cell viability. The cell viability continued to decline when the time went to 72nd hour, and the Salvia treatment group had more benefit than Astragalus and combined treatment.2. Effects of Salvia and Astragali on the transcriptions of mRNA of calcium handing proteinsUseing RT-PCR method observed at different time points (24h,48h,72h) Salvia and Astragali on the transcriptions of mRNA of calcium handing protein SERCA2a and PLB mRNA Results1.24th hour, compared with the SERC A2a, PLB mRNA transcription level, SERCA2a/PLB rates of normal group, the model group had decreased, but not statistically significant compared to the normal group. DS group could raise the level of PLB mRNA transcription, down SERCA2a/PLB ratio. HQ group can raise SERCA2a, PLB mRNA transcription level, SERCA2a/PLB ratio. DQ group can down SERCA2a, PLB mRNA transcription level, up SERCA2a/PLB ratio.2.48th hour, compared with the normal, model group's SERCA2a, PLB mRNA transcription level, SERCA2a/PLB ratio, still showing a downward trend's group raised the level of SERCA2a mRNA transcription, reduced PLB mRNA transcription level, up SERCA2a/PLB ratio to normal levels. HQ group increased SERCA2a mRNA transcription, reduced the level of PLB mRNA transcription, and was significantly up SERCA2a/PLB ratio. DQ group continued to fall SERCA2a, PLB mRNA transcription level, up SERCA2a/PLB ratio.3.72nd hour, compared with the normal, transcription level of SERCA2a, PLB mRNA transcription levels decreased more significantly, SERCA2a/PLB rate of decline picked up. DS group is up SERCA2a, PLB mRNA transcription level, SERCA2a/PLB ratio. HQ group raised the level of SERCA2a mRNA transcription, but transcription of the PLB mRNA levels continued to play down, the role of the SERCA2a/PLB rate was still significantly increased. DQ group increased SERCA2a mRNA transcription level of effect is obvious, on the PLB mRNA transcription level of up trend, significantly increases SERCA2a/PLB ratio.ConclusionAng II causes the myocardial cell dynamic changes of survival ratio during the process of hypertrophy to heart failure, and causing cardiac sarcoplasmic reticulum calcium transport proteins dynamic changes of mRNA transcription, protein expression levels. Those affect the intracellular calcium ion concentration,thus affecting the changer of normal calcium transient. Note to Ang II could induce the changes of transcription and expression of calcium handing protein resulting in sarcoplasmic reticulum calcium transport barriers. This progress can be inhibitited by Salvia and Astragali. Salvia and Astragali not only protect the heart's overall function, but also has a protective effect in a single cardiac cell contraction, during the long course of treatment in CHF. They also can antagonize the abnormal changes of calcium transient and calcium handing protein in heart failure. In the summary, the effect of Salvia and Astragali on anti-heart failure, partly by regulating the changes of calcium transient and calcium handing protein, thereby improving the calcium transient in cardiac cells, resulting in shrinkage of cardiac cells are protected. |
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