兔甲亢性心肌病不同左室构型心肌细胞的凋亡

目的:观察兔甲亢性心肌病不同左室构型心肌细胞的凋亡情况及相关bcl 2、bax蛋白表达的变化。方法: 将30只新西兰纯种白兔分为实验组(n=20)和对照组(n=10)，实验组兔每日腹腔注射左旋甲状腺素(45 μg/kg体质量)共4周建立甲亢动物模型，对照组兔每日腹腔注射同等剂量的生理盐水共4周。4周后，对两组兔行常规超声心动图参数测定。实验组依据超声参数又分为向心性肥厚亚组(CH亚组)和离心性肥厚亚组(EH亚组)。第4周末处死所有兔，取心肌组织，在透射电镜下观察心肌细胞，应用原位末端标记法标记凋亡的心肌细胞，应用免疫组织化学染色法检测bcl 2、bax蛋白的表达。结果: ①透射电镜观察CH亚组和EH亚组均有大量的凋亡细胞，且凋亡指数(AI)显著高于对照组(均P<001)，EH亚组的AI又显著高于CH亚组(P<001)。②CH亚组和EH亚组bcl 2蛋白的表达显著低于对照组(均P<001)，EH亚组又显著低于CH亚组(P<001)；CH亚组和EH亚组bax蛋白的表达显著高于对照组(均P<001)，EH亚组又显著高于CH亚组(P<001)。CH亚组和EH亚组bcl 2/bax的比值显著低于对照组(均P<001)。结论: 兔甲亢性心肌病不同左室构型具有不同程度的心肌细胞凋亡，说明细胞凋亡机制参与了该病的病理过程，其作用与下调bcl 2蛋白的表达、上调bax蛋白的表达有关。

Cardiomyocyte apoptosis of different left ventricular geometric patterns in rabbits with hyperthyroid cardiomyopathy

AIM:To study cardiomyocyte apoptosis and the expressions of bcl 2 and bax protein in levothyroxine induced 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 (L Thy) 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 transferase mediated dUTP nick end labeling (TUNEL) method and the expressions of bcl 2 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<001). The index in apoptotic cardiomyocytes of the EH subgroup was higher than in the CH subgroup (P<001). Compared with the control group, bcl 2 protein expression was significantly lower in the CH subgroup and EH subgroup (P<001) and bcl 2 protein expression in the EH subgroup was lower than in the CH subgroup (P<001). The expression of bax protein was significantly higher in the CH subgroup and EH subgroup (P<001) and bax protein expression in the EH subgroup was higher than in the CH subgroup (P<001); bcl 2/bax was significantly lower in CH subgroup and EH subgroup (P<001). CONCLUSION: The degree of cardiomyocyte apoptosis is different in different patterns of left ventricular geometric models of levothyroxine induced cardiomyopathy, indicating that cardiomyocyte apoptosis is an important pathological mechanism of levothyroxine induced cardiomyopathy. The effect may be related to the downregulation of bcl 2 protein expression and upregulation of bax protein expression.