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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(45μg/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。
AIM: To observe the changes of apoptosis and the expression of bcl-2 and bax proteins in different left ventricular cardiomyocytes of hyperthyroid cardiomyopathy in rabbits. Methods: Thirty New Zealand white rabbits were divided into experimental group (n = 20) and control group (n = 10). The experimental group were given daily intraperitoneal injection of levothyroxine (45μg / kg body weight) for 4 weeks to establish hyperthyroidism Animal model, the control group rabbits were injected intraperitoneally with the same dose of normal saline for 4 weeks. Four weeks later, routine echocardiographic parameters were measured in two groups of rabbits. Experimental group based on ultrasound parameters are further divided into concentric hypertrophy subgroup (CH subgroup) and eccentric hypertrophy subgroup (EH subgroup). At the end of the 4th week, all the rabbits were sacrificed and the myocardial tissue was taken out. The cardiomyocytes were observed under transmission electron microscope. Apoptotic cardiomyocytes were labeled by end-terminal labeling method. The expression of bcl-2 and bax protein was detected by immunohistochemical staining. Results: (1) There were a large number of apoptotic cells in the CH subgroup and the EH subgroup, and the apoptotic index (AI) was significantly higher than that of the control group (all P <0.01). The AI of EH subgroup was significantly higher than that of CH Subgroup (P <0.01). ② The expression of bcl-2 protein in CH and EH subgroups was significantly lower than that in control group (all P <0.01), while EH subgroup was significantly lower than CH subgroup (P <0.01) (P <0.01). The EH subgroup was significantly higher than that of CH subgroup (P <0.01). The ratio of bcl-2 / bax in CH subgroup and EH subgroup was significantly lower than that in control group (all P <0.01). CONCLUSION: Different LV structures of rabbit hyperthyroidism cardiomyopathy have different degree of cardiomyocyte apoptosis, indicating that the mechanism of apoptosis is involved in the pathological process of the disease, which may be related to the down-regulation of bcl-2 protein expression and up-regulation of bax protein expression related.