| Chronic heart failure is the end-stage expression of various kinds of heart disease, and it is a major cause death for patients with heart problem. In recent years, with increasing of the incidence rate of coronary heart disease and hypertension, the incidence rate of chronic heart failure began to rise. Chronic heart failure already became one of the severe disease that threatens human health. Myocardial fibrosis is the most important pathological basis of chronic heart failure. Therefore, prevention and control of the myocardial fibrosis have become the focus of research these years. A series of cell factors facilitating inflammation played an important role in the myocardial fibrosis occur and development process. The transforming growth factor-β1(TGF-β1) and connective tissue growth factor (CTGF) has attracted much attention in recent years. In this study, chronic heart failure model was developed in rats by abdominal aortic constriction, and then investigated the dynamic expression and significance of TGF-β1and CTGF in the occurred and development of myocardial fibrosis in rats.Objective:The model of myocardial fibrosis in rats with chronic heart failure was established by abdominal aortic constriction, and investigated the dynamic expression of TGF-β1and CTGF in myocardium of rats with myocardial fibrosis induced by pressure overload in cellular and molecular level by immunohistochemiscal staining and RT-PCR.Methods:1Randomly provide8rats from42male Wistar rats as sham-operated group (sham group), and other rats were made chronic heart failure model by abdominal aortic constriction, and the left ventricular end diastolic pressure (LVEDP)≥15mmHg was taken as standard. When the chronic heart failure model was successfully established, residues were randomly divided into3groups, HF1d group, HF7d group, HF14d group, and8rats in each group. The rats in sham group were operated in the same way as others except for no aortic constriction.2Hemodynamic parameters LVEDP and the maximum change rate of left ventricular pressure rise and fall (±dp/dtmax) were examined by multi-lead electric physiological instrument at the end points of each group, and taken the left ventricle to calculation the left ventricular mass index (LVMI).3HE and Masson staining were used to observe histopathological change of left ventricular myocardium, and to detect the collagen volume fraction (CVF) in each group.4Transmission electron microscope was used to observe the ultrastructure of left ventricular myocardium.5SP immunohistochemical staining was used to observe the expression of TGF-β1and CTGF protein in left ventricular myocardium.6RT-PCR was used to detect the expression of TGF-β1and CTGF mRNA in left ventricular myocardium.Results:1Hemodynamic parameters in each group:The LVEDP in HF1d group, HF7d group, HF14d group were (15.56±1.69) mmHg,(17.87±2.19) mmHg and (20.03±1.93) mmHg, which increased singnificantly compared with rats in sham group (P<0.01). The±dp/dtmax in model groups were (4673.62±206.63) mmHg/s,(3339.74±238.65) mmHg/s;(4360.26±239.65) mmHg/s,(3091.85±245.24) mmHg/s;(4120.59±215.13) mmHg/s,(2860.20±199.73) mmHg/s. Compared with sham group, the±dp/dtmax in model groups were obvious decreased (P<0.01). As the time of heart failure elongated, the degree of left ventricular function worsening aggravated.2Histopathological change of left ventricular myocardium in each group: HE staining:In sham group, the arrangement of myocardial fibers were compact and orderliness, the appearance of myocardial cells were normal, and the cytoplasm texture was clear. For model groups, with the time of heart failure elongated, the myocardium show:the myocardial cells were swelling and degeneration, the myocardial fibers were waved even fracture. MAS SON staining:there was not obviously collagen deposition in sham group. For model groups, the collagen deposition increased gradually with the time of heart failure elongated.3LVMI and CVF in each group:The LVMI and CVF in HF1d group, HF7d group, HF14d group were (2.53±0.17)%o,(15.62±1.83)%;(2.86±0.28)%o,(22.31±2.34)%;(3.15±0.26)%o,(25.12±2.96)%. The indexes in model group was higher than that in sham group (P<0.01), and it increased gradually with the time of heart failure elongated.4Ultrastructure of left ventricular myocardium observed in each group:In the sham group, the arrangement of myofibrils were orderliness, the zone Z was clear. The structure of mitochondria was integrated. There was only a little collagen deposition in the myocardial interstitial. In the model groups, the myofibrils were disarranged, the structure of sarcomere was unclear, the zone Z was partly disappeared, the cristae of mitochondria was swollen and partly dissolved. The collagen deposition increased gradually with the time of heart failure elongated.5TGF-β1expression in left ventricular myocardium of rats:TGF-β1immunopositive products were buffy granules and located in cytomembrane and interstitial tissue of myocardium, mainly at interstitial tissue. Compared with sham group rats, the TGF-β1protein and mRNA expression in myocardium of rats in model groups increased obviously (P<0.01), and it increased gradually with the time of heart failure elongated. There had significantly differences in model groups (P<0.01, P<0.05).6CTGF expression in left ventricular myocardium of rats:CTGF immunopositive products were buffy granules and located in cytoplasm and interstitial tissue of myocardium, mainly at cytoplasm. Compared with sham group rats, the CTGF protein and mRNA expression in myocardium of rats in model groups increased obviously (P<0.01, P<0.05), and it increased gradually with the time of heart failure elongated. There had significantly differences in model groups (P<0.01).Conclusions:1The model of myocardial fibrosis with chronic heart failure in rats was successfully established by abdominal aortic constriction, and it is in accordance with the pathological process of human myocardial fibrosis.2The expression of TGF-β1and CTGF in left ventricular myocardium was increased in myocardial fibrosis of rats with chronic heart failure, and its level is related closely to the severity of chronic heart failure. |
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