Cardiomyocyte apoptosis of different left ventricular geometric patterns in rabbits with hyperthyroid cardiomyopathy
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Graphical Abstract
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Abstract
AIM:To study cardiomyocyte apoptosis and the expressions of bcl2 and bax protein in levothyroxineinduced cardiomyopathy in rabbits with different patterns of left ventricular geometric models. METHODS: Thirty New Zealand purebred rabbits were stochastically divided into experimental group (n=20) and control group (n=10). Hyperthyroidism models were established by peritoneal injection of levothyroxine (LThy) in experimental group [45 μg/(kg·day)] for 4 weeks. The same dose of saline was given to rabbits in the control group for 4 weeks. Conventional echocardiographic parameters were obtained at the end of the fourth week in both groups and according to the changes of ultrasound parameters, the rabbits of experimental group were divided into two subgroups: concentric hypertrophy (CH) and eccentric hypertrophy (EH). All rabbits were executed 4 weeks later, myocardial tissue was obtained and cardiomyocytes were observed by transmission electron microscope. Apoptotic cardiomyocytes were detected using terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) method and the expressions of bcl2 and bax protein were determined by immunohistochemical method using mean absorbance. RESULTS: Many apoptotic cardiomyocytes were found in CH subgroup and EH subgroup by electron microscope, whereas no apoptotic cardiomyocytes were seen in the control group. Compared with that in the control group, the index of apoptotic cardiomyocytes increased significantly in both subgroups (P<001). The index in apoptotic cardiomyocytes of the EH subgroup was higher than in the CH subgroup (P<001). Compared with the control group, bcl2 protein expression was significantly lower in the CH subgroup and EH subgroup (P<001) and bcl2 protein expression in the EH subgroup was lower than in the CH subgroup (P<001). The expression of bax protein was significantly higher in the CH subgroup and EH subgroup (P<001) and bax protein expression in the EH subgroup was higher than in the CH subgroup (P<001); bcl2/bax was significantly lower in CH subgroup and EH subgroup (P<001). CONCLUSION: The degree of cardiomyocyte apoptosis is different in different patterns of left ventricular geometric models of levothyroxineinduced cardiomyopathy, indicating that cardiomyocyte apoptosis is an important pathological mechanism of levothyroxineinduced cardiomyopathy. The effect may be related to the downregulation of bcl2 protein expression and upregulation of bax protein expression.
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