| Heart failure is a variety of heart disease, leading to heart structure or function of abnormalities and ventricular filling or pumping blood disorders with fatigue, shortness of breath and fluid retention as the main clinical manifestations of the syndrome, is the end stage of a variety of cardiovascular diseases. In China, there are about 4 million heart failure patients, 5-year survival rate is only 33%, which is similar to tumors. In developed countries, heart failure has become the main reason for adult deaths. Although modern medicine can control the development of heart failure, the life quality of patients is seriously declined. With the continuous development of integrative medicine, the traditional Chinese medicine has made certain advantages in controlling symptoms, improving life quality of patients and the prognosis and so on. Herbs for tonifying qi is widely used in traditional Chinese medicine when treating heart failure.In cardiac myocytes, calcium can participate in excitation-contraction coupling by changing instant intracellular concentrations, making the formation of calcium transient. Calcium transient changes are the cellular basis of cardiac dysfunction. In most cases, abnormal calcium transients can occur before myocardial systolic and diastolic function decreased. Many previous studies showed that the qi-tonifying herbs can correct the abnormal calcium transients. Therefore, correcting calcium transient abnormalities may be one of the mechanisms of qi-tonifying herbs in treating heart failure.PurposeTo explore the effects of qi-tonifying herbs on heart failure intracellular calcium transients by creating mouse models by narrowing thoracic aorta and treating them with different qi-tonifying herbs.MethodWe created mouse models by narrowing the thoracic aorta, then devided them into six groups:model group, control group, astragalus group, ginseng group, codonopsis group, the metoprolol group (tartaric acid metoprolol). After 4-week treatment, we measured and recorded the thickness of heart wall, ejection fraction and E/Ea value by ultrasound; recorded calcium transients by laser amplitude confocal microscopy; detected the expression level of CAMKII by Western Blot.Results1. The left ventricular structure:compared with control group, the left ventricular weight, left ventricular posterior wall at end-diastole(LVPWd) in model group were obviously increased (P<0.05), the left ventricular anterior wall at end-diastole (LVAWd) was significantly increased (P<0.01). And each group compared with model group after the treatment, the left ventricular weight and LVAWd in codonopsis group were decreased obviously (P<0.05); LVPWd in metoprolol group was obviously improved (P<0.05).2. The left ventricular function:Compared with the control group, ejection fraction (EF), fractional shrinkage (FS), atrial systolic velocity and E/Ea values in model group were significantly decreased (P<0.01). Compared with model group, EF and FS in the astragalus, codonopsis groups were increased obviously (P<0.05); left ventricular internal diameter at end-systolic in condonposis group was decreased obviously (P<0.05); E/Ea values were obviously improved in astragalus group (P<0.05).3. Calcium transient in classic Tyrode’s salts solution:compared with control group, the height of calcium transient, time for dropping down, constant, SR leak in model group were significantly damaged (P<0.01). Compared with model group, astragalus, codonopsis and metoprolol can increase the height of calcium transients obviously (P<0.05); astragalus, ginseng, codonopsis and metoprolol can short the time for dropping down obviously (P<0.05); astragalus, ginseng and codonopsis can inhibit the SR leak (P<0.05).4. Calcium transients in Tyrode’s salts solution with isopropyl:Compared with the control group, the height of calcium transients and time for dropping down were significantly damaged (P<0.01). Compared with model group, astragalus can imcrease the height of calcium transients significantly (P<0.01); asragalus, codonopsis and metoprolol can short the time for dropping down significantly (P<0.01).5. Force Frequency relationship:when the frequency was 2.0hz, compared with the control group, the height of calcium in model group was increased obviously (P<0.05); compared with the model group, the ginseng and metoprolol can decrease the height of calcium transient (P<0.05).6. Western Blot:compared with the control group, expression level of CAMKII were obviously decreased (P<0.05). Compared with model group, asragalus, ginseng, codonopsis, metoprolol can decrease the level of CAMKII significantly (P<0.01).Conclusion1. By improving calcium transients is one of the mechanisms for qi-tonifying herbs treating heart failure, and different qi-tonifying herbs improve different indicators.2. All qi-tonifying herbs can inhibit the expression of CAMKII and SR leak, shorten time for calcium transients dropping down, improve systolic and diastolic function under stress; ginseng can inhibit force frequency relationship, while codonopsis can increase the height of calcium transient, inhibit ventricular remodeling at the same time.3. Based on the above two points, the different compatibility between qi-tonifying herbs appropriately may increase the clinical effect, more comprehensive improvement in various indicators of heart failure. |
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