| Heart failure is influenced by the neuroendocrine and cytokine activation and ventricular remodeling. The development of neuroendocrine activation plays a central role in heart failure, the continued activation of these systems leads to cardiac hypertrophy, apoptosis, and ventricular remodeling and fibrosis. Ventricular remodeling leading to continued progress in the pathophysiology of heart failure based on a series of complex molecular and cellular mechanisms leading to myocardial structure, function and phenotypic changes. Calcium homeostasis, changes in protein synthesis and cell apoptosis of ventricular remodeling, are important factors in the development and outcome, and therefore the progress and prognosis of heart failure. Cardiomyocyte apoptosis in the maintenance of normal cardiac morphology has great significance, and in the heart of the physiology and pathology plays an important role in the development process, is considered as the basis of cytology in the changes of heart from compensated to decompensated.Endoplasmic reticulum is an important site of the regulation of calcium homeostasis, and protein, lipid synthesis in the body, and called the endoplasmic reticulum system as sarcoplasmic reticulum within the myocardial cells. The physical and chemical changes in the environment around sarcoplasmic reticulum can result in unfolding/misfolding protein aggregation and calcium regulation disorders, dysfunction of the endoplasmic reticulum, known as endoplasmic reticulum stress. Moderate endoplasmic reticulum stress favor of restoration of myocardial cells and repair damage from the steady. Persistent and severe endoplasmic reticulum stress have resulted in sarcoplasmic reticulum calcium homeostasis disorder, endoplasmic reticulum stress-related triggers apoptosis, compensatory shift caused by the failure of myocardial cells, and is an important molecular mechanism of heart failure.The current mode of treatment for heart failure improvement from a simple turn inhibit the hemodynamic turn to inhibit RASS and sympathetic nervous system activation, aims to reverse ventricular remodeling and improve long-term prognosis. But still not prevent the occurrence and development of heart failure fundamentally.Major role in growth hormone is to promote growth and development and impact of metabolism, past mainly for the treatment of children with growth hormone deficiency. Growth hormone has been found in recent years in the maintenance of normal cardiovascular function has an important physiological role. Growth hormone can improve cardiac contractility, this effect has been recognized in the past for the heart failure caused by dilated cardiomyopathy. Growth hormone has been present in some clinical trials in heart failure patients showed improvement in cardiac function role. But in fact the exact mechanism of its anti-heart failure is not very clear, especially due to ischemic heart failure after myocardial infarction.By ligation the left anterior descending branch of rats, this study established animal model of ischemic heart failure, selected modeling survival after 4 weeks 20 rats were randomly divided into 2 groups:10 rats in heart failure group,10 rats in growth hormone group, from the 5th weeks, rats in growth hormone group were given growth hormone on 2U/kg weight,1/d subcutaneously. And set up sham operation group of 10 rats for thoracic surgery and string under the coronary artery but not ligate. All rats were normal raised for 8 weeks after surgery. After 8 weeks, hemodynamic parameters were observed, and the results showed, compared with heart failure, growth hormone group were significantly decreased LVEDP,±dp/dt were significantly recovered, indicating that growth hormone can improve ischemic heart failure systolic and diastolic heart function in rats. Rats were sacrificed to observe the rat heart, the intervention of a certain degree of growth hormone to maintain the general structure of the normal heart, myocardial cells by light microscopy the structure of growth hormone group was significantly improved compared with heart failure, left ventricular interstitial and significantly reduced the proliferation of collagen fibers, HW/BW, LVW/BW significantly lower than the heart failure group, no significant difference with the sham group, indicating that growth hormone significantly inhibited the incidence of left ventricular remodeling.Serum levels of AngⅡand BNP in growth hormone group were significantly decreased compared with heart failure group, confirmed the growth hormone effective to reduce the RAAS further impact on the heart, reducing left ventricular remodeling and improve cardiac function in rats with ischemic heart failure, neuroendocrine factors and to mitigate further impact on the heart.Immunohistochemistry and Western-blot results showed that the myocardium in the heart failure group was significantly higher in Caspase-3 that ischemic myocardial apoptosis in heart failure significantly increased. Growth hormone group decreased Caspase-3 prove that growth hormone can significantly reduce the level of cardiomyocyte apoptosis. Immunohistochemistry and PCR results showed that heart failure group compared with sham group decreased expression of Bcl-2 protein, mRNA content decreased, Bax increased protein expression, mRNA levels increased, Bcl-2/Bax ratio was significantly decreased, indicating that in heart failure intensified the process of cardiomyocyte apoptosis, and promote apoptosis. Growth hormone intervention raised the expression of Bcl-2 protein level, Bax protein was decreased, Bcl-2/Bax ratio was significantly increased compared with heart failure, this intervention results showed that growth hormone inhibited the myocardial cells in ischemic heart failure apoptosis, helps to maintain normal cardiac structure and function of cells.Myocardial tissue of heart failure was significantly reduced SERCA2a, sarcoplasmic reticulum calcium transport capacity decreased, causing the sarcoplasmic reticulum Ca2+ uptake rate of decline and intake decreased cytoplasmic calcium concentration, leading to relaxation of myocardial cells function decline, growth hormone intervention SERCA2a expression was significantly increased, transit calcium capacity enhancement, sarcoplasmic reticulum of Ca2+ uptake to speed, intake increased sarcoplasmic reticulum calcium concentration increased myocardial diastolic function was improved, the heart function was improved.In the ischemic state, the sarcoplasmic reticulum homeostasis imbalance, resulting in endoplasmic reticulum stress response, excessive activation of endoplasmic reticulum stress in the endoplasmic reticulum of the cytoplasm side of Caspase-12, and through the Caspase-12 initiate apoptosis. Myocardial cells in heart failure Caspase-12 expression was significantly increased, the same as the changes of Caspase-3, indicating that ischemic heart failure led to endoplasmic reticulum stress, continued activation of the endoplasmic reticulum stress Caspase-12, the order of activation of Caspase -3 leading to apoptosis. GH inhibited the activation of Caspase-12, blocking the endoplasmic reticulum stress-induced apoptosis pathway, thereby reducing ischemic myocardial apoptosis in heart failure.In summary, this paper confirms the growth hormone can reduce ventricular remodeling in rats with ischemic heart failure, cardiac systolic and diastolic function improve, control of ischemic heart failure. Anti-heart failure mechanism of growth hormone is that growth hormone can stabilize sarcoplasmic reticulum function in myocardial cell of ischemic heart failure and enhance the expression of SERCA2a, maintaining calcium homeostasis in myocardial cells and improve myocardial systolic and diastolic function. And by inhibiting the activation of Caspase-12, blocking the endoplasmic reticulum stress-induced apoptosis pathway, reducing the expression of Caspase-3, so that the expression of Bcl-2 levels rise, Bax protein was decreased, Bcl-2/Bax ratio increased, play a role in inhibiting apoptosis of myocardial cells. |
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