雌激素对异丙肾上腺素诱导的大鼠心肌损伤及心肌细胞凋亡的影响

Effect of estrogen on cardiac injury and cardiomyocyte apoptosis of rat induced by isoproterenol

目的通过建立大鼠双侧卵巢切除及异丙肾上腺素诱导的心肌损伤模型,研究雌激素对异丙肾上腺素致大鼠心肌损伤及心肌细胞凋亡的影响。方法 50只雌性SD大鼠行双侧卵巢切除术和假手术后分为5组(每组10只):假手术组(Sham组);双侧卵巢切除组(OVX组);心肌损伤组(OVX+ISO+Vehi组),雌激素4μg·kg-1·d-1治疗组(OVX+ISO+E2a组),雌激素40μg·kg-1·d-1治疗组(OVX+ISO+E2b组)。分别测量大鼠大体指标,颈总动脉置管监测心脏血流动力学参数,分离培养单个心肌细胞观察形态与收缩功能改变,以及蛋白免疫印迹法检测心肌细胞凋亡蛋白的表达。结果异丙肾上腺素明显降低心肌功能,增加心肌细胞肥大与凋亡,降低单个心肌细胞收缩功能(P<0.05)。高剂量雌激素(40μg·kg-1·d-1)替代治疗显著改善异丙肾上腺素引起的心肌损伤与心肌功能下降(P<0.05),并通过增加Bcl-2蛋白表达,减少Bax蛋白表达与Caspase-3的激活,降低心肌细胞肥大与凋亡(P<0.05)。而低剂量雌激素(4μg·kg-1·d-1)只表现出轻度抗异丙肾上腺素心肌损伤的作用,但差异无统计学意义(P>0.05)。结论适宜剂量的雌激素替代治疗通过降低心肌细胞凋亡,提高心肌细胞收缩功能,从而对异丙肾上腺素诱导的心肌损伤发挥保护作用。

Objective To study the effect of estrogen on cardiac injury and cardiomyocyte apoptosis of rat induced by isoprotere-nol by modeling cardiac inj ury induced by bilateral ovariectomized （OVX）and isoproterenol （ISO）.Methods Fifty female SD rats with bilateral ovariectomy and sham operation （Sham）were randomly divided into 5 groups：sham operation group （Sham group）, bilateral ovariectomy group （OVX group）,cardiac injury group （OVX＋ISO＋Vehi group）,low dose estrogen treatment group （OVX＋ISO＋E2 a group,4μg·kg^-1 ·d^-1 ）,high dose estrogen treatment group （OVX＋ISO＋E2 b group,40μg·kg^-1·d^-1 ）. these status were separately measured：rats′general features,hemodynamics parameters monitored of carotid artery,morphological observation and cardiomyocyte contraction change of single-cardiomyocyte separate cultured,cardiomyocyte apoptosis protein ex-pression were detected by immunoblotting.Results ISO significantly reduced myocardial pump function,increased hypertrophy and apoptosis of cardiomyocytes,reduced contractility of single cardiomyocytes （P〈0.05）.High-dose estrogen （40μg·kg^-1·d^-1 ） replacement therapy significantly improved ISO induced cardio inj ury and cardio functions decreasing,also inhibited Bax expression and caspas-3 activation and decreased myocardial hypertrophy and cardiomyocytes apoptosis through increasing Bcl-2 expression （P〈0.05）,significantly.while low dose estrogen （4μg·kg^-1·d^-1 ）treatment showed marginally protection effects on ISO in-duced cardio inj ury with no statisticly significance.Conclusion Appropriate dose estrogen replacement therapy can decrease cardio-myocyte apoptosis,improve cardiomyocytes contractility,so as to protect ISO-induced cardiomyocyte apoptosis.