Abstract：
BACKGROUND: Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β2-adrenergic receptor (β2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.
OBJECTIVE: The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.
METHODS: Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.
RESULTS: The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.
CONCLUSIONS: Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.
OBJECTIVE: The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.
METHODS: Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.
RESULTS: The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.
CONCLUSIONS: Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.
摘要：
背景：目前，在临床上没有有效的治疗Takotsubo综合征（人类应激引起的心脏损伤）。先前已显示β2-肾上腺素能受体（β2-AR）激动剂福莫特罗可减少实验性takotsubo综合征中的心肌细胞损伤。
目的：本研究的目的是研究福莫特罗是否能预防应激性心肌病中心肌细胞和内皮细胞的凋亡和坏死。
方法：通过固定大鼠2、6和24小时来诱导应激诱导的心脏损伤。
结果：应激大鼠的心肌表现出收缩性降低和心肌细胞损伤的组织学表现：核缩，心肌细胞和内皮细胞的核周水肿，微循环干扰随着压力的延长而增加。此外,在应激开始后6小时检测到内皮细胞凋亡，并在24小时达到峰值。仅在压力暴露24小时后，心肌细胞的凋亡才显着增加。这些形态学改变与血清肌酸激酶-MB水平升高有关，紧张24小时后，syndecan-1和血栓调节蛋白。在24小时的压力暴露期间四次施用β2-AR激动剂福莫特罗（50μg/kg）导致心肌收缩性改善，组织学特征的严重程度降低，TUNEL阳性心肌细胞数量减少，血清肌酸激酶-MB，syndecan-1和血栓调节蛋白水平。
结论：目前的数据表明，在应激诱导的心脏损伤中，心肌细胞的凋亡和坏死以及内皮细胞的坏死可以通过激活β2-AR来减轻。然而,福莫特罗不能完全消除心肌细胞凋亡，组织学改变，或应激下的内皮损伤标志物。
目的：本研究的目的是研究福莫特罗是否能预防应激性心肌病中心肌细胞和内皮细胞的凋亡和坏死。
方法：通过固定大鼠2、6和24小时来诱导应激诱导的心脏损伤。
结果：应激大鼠的心肌表现出收缩性降低和心肌细胞损伤的组织学表现：核缩，心肌细胞和内皮细胞的核周水肿，微循环干扰随着压力的延长而增加。此外,在应激开始后6小时检测到内皮细胞凋亡，并在24小时达到峰值。仅在压力暴露24小时后，心肌细胞的凋亡才显着增加。这些形态学改变与血清肌酸激酶-MB水平升高有关，紧张24小时后，syndecan-1和血栓调节蛋白。在24小时的压力暴露期间四次施用β2-AR激动剂福莫特罗（50μg/kg）导致心肌收缩性改善，组织学特征的严重程度降低，TUNEL阳性心肌细胞数量减少，血清肌酸激酶-MB，syndecan-1和血栓调节蛋白水平。
结论：目前的数据表明，在应激诱导的心脏损伤中，心肌细胞的凋亡和坏死以及内皮细胞的坏死可以通过激活β2-AR来减轻。然而,福莫特罗不能完全消除心肌细胞凋亡，组织学改变，或应激下的内皮损伤标志物。
