Effect Of Anti-heart-failure â…¡ Granules On Of Rats And The Mechanism Research

Objective:To observe the intervening effect of Anti-heart-failure Ⅱ granules in Diastolic Heart Failure (DHF) rat model. DHF model is established prior to treatment intervention. The findings of treatment group and control group are subsequently observed and compared. The effects and mechanisms of the drug Anti-heart-failure Ⅱ granules in treating DHF are explored and discussed.Methods:DHF rat model was established using the abdominal aorta coarctation method, and randomly divided into model group, positive drug group, Anti-heart-failure Ⅱ granules in large, medium and small dosage group, and sham operation group was also established. After for8-week dosage, echocardiography and cardiac catheterization were employed to detect the indices of rat cardiac functions, and the effects of Anti-heart-failure Ⅱ granules on DHF rats were observed through the following methods:DHF rat cell structure and collagen content via HE staining, Masson staining and transmission electron microscope observation; myocardial cells of DHF rats calcium ion (Ca2+) via Confocal laser scanning microscopy observation. Similarly, detection of calcium ion-ATP enzyme (Ca2+-ATPase) and Na+-K+-ATP enzyme (Na+-K+-ATPase) activities were determined through the same device. These aid in the observation of the effect of Anti-heart-failure Ⅱ granules on DHF rats’ cardiac muscle Ca2+transport and energy metabolism; plasma rennin activity (PRA), angiotensin Ⅰ (AT-Ⅰ), angiotensin Ⅱ (AT-Ⅱ) and aldosterone (ALD) were determined to observe the effect of Anti-heart-failure Ⅱ granules on DHF rats’Renin Angiotensin Aldosterone System (RAAS); immunofluorescence confocal microscopy was used to observe intracellular transforming growth factor β1(TGF-β1), and quantitative Western Blot assay for the detection of intracellular TGF-beta1, tumor necrosis factor alpha (TNF-a), collagen type Ⅰ (collagen Ⅰ) and collagen type Ⅲ (collagen Ⅲ). The mechanisms of Anti-heart-failure Ⅱ granules granule in the treatment of DHF from the above aspects were investigated.Results:(1) Compared with the normal group, the rats in the model group showed an increase (P<0.05) in mitral valve early diastolic peak velocity (E) to mitral annular early diastolic velocity(e) ratio (E/e), an increase (P<0.01) in left ventricular end diastolic pressure (LVEDP) and left ventricular relaxation time constant (Tau), decrease (P<0.01) in the internal pressure of left ventricle both maximum rise and drop rate (±LVdp/dtmax), and a remarkable increase (P<0.01) in the left ventricular index, with myocardial cell hypertrophy and vacuolation, enlarged nuclei or co-liquefaction, muscle fiber broadening and an interval space enlargement. Comparing with the model group, Anti-heart-failure II granules can reduce E/e (P<0.05), decrease LVDEP and Tau (P<0.01), increase±dp/dtmax (P<0.05), decrease left ventricular index (P<0.01), and reduce the degree of myocardial cell lesion.(2) Compared with the sham operation group, the plasma PRA, ALD in model group increased (P<0.05), while AT-Ⅱ increased significantly (P<0.01). Compared with the model group, benazepril group and Anti-heart-failure Ⅱ granules in high dose group saw a decrease in AT-Ⅱ (P<0.05), benazepril group and Anti-heart-failure Ⅱ granules in mid and high dose group saw lower ALD as well (P<0.05).(3) Compared with the sham operation group, the fluorescence intensity reflecting myocardial intracellular concentration of Ca2+increased in the model group, and Ca2+-ATPase activity decreased (P<0.05). Compared with the model group, benazepril group and Anti-heart-failure Ⅱ granules groups effectively increased the activity of Ca2+-ATPase (P<0.01), decreasing the intracellular Ca2+concentration (P<0.01).(4) Compared with the sham operation group, Na+-K+-ATPase activity decreased (P<0.05) in the model group, with myocardial mitochondria edema, structural damage and sarcoplasmic reticulum dilatation of terminal cistern observed. No significant difference was found between the activity of Na+-K+-ATPase in benazepril group and model group. Anti-heart-failure Ⅱ granules in mid and high dose group showed higher Na+-K+-ATP enzyme activity compared with the model group (P<0.01), while mitochondrial lesions was less severe than the model group.(5) Myocardial intracellular TGF-β1expression increased in the model group rats (P<0.05), while TNF-α and collagen Ⅰ and Ⅲ were significantly increased (P<0.01), and Masson staining showed collagen deposition. Compared with the model group, benazepril group and CHF Ⅱ granule groups were able to inhibit the expression of TGF-β1, TNF-α and collagen Ⅰ and Ⅲ (P<0.05), Masson staining showed less collagen deposition than the model group.Conclusion:Anti-heart-failure Ⅱ granules could improve cardiac diastolic function in DHF rats. This mechanism may be functioning through the inhibiting of RAAS activation, reversal of myocardial fibrosis, enhancing myocardial intracellular Ca2+transportation and improving energy metabolism.