CAJ | 학술논문

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＋E2 a组），雌激素40μg·kg－1·d－1治疗组（OVX＋ISO＋E2 b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。
목적：통과건립대서쌍측란소절제급이병신상선소유도적심기손상모형，연구자격소대이병신상선소치대서심기손상급심기세포조망적영향。방법50지자성 SD대서행쌍측란소절제술화가수술후분위5조（매조10지）：가수술조（Sham조）；쌍측란소절제조（OVX조）；심기손상조（OVX＋ISO＋Vehi조），자격소4μg· kg－1· d－1치료조（OVX＋ISO＋E2 a조），자격소40μg·kg－1·d－1치료조（OVX＋ISO＋E2 b조）。분별측량대서대체지표，경총동맥치관감측심장혈류동역학삼수，분리배양단개심기세포관찰형태여수축공능개변，이급단백면역인적법검측심기세포조망단백적표체。결과이병신상선소명현강저심기공능，증가심기세포비대여조망，강저단개심기세포수축공능（P＜0．05）。고제량자격소（40μg·kg－1·d－1）체대치료현저개선이병신상선소인기적심기손상여심기공능하강（P＜0．05），병통과증가 Bcl-2단백표체，감소 Bax단백표체여 Caspase-3적격활，강저심기세포비대여조망（P＜0．05）。이저제량자격소（4μg·kg－1·d－1）지표현출경도항이병신상선소심기손상적작용，단차이무통계학의의（P＞0．05）。결론괄의제량적자격소체대치료통과강저심기세포조망，제고심기세포수축공능，종이대이병신상선소유도적심기손상발휘보호작용。
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.