Analysis of brain-heart interaction in response to emotional stress using animal model of psychosomatic disease

绝经后女性Tako-tsubo型心肌病主要表现为心电ST段抬高和左室心尖肿胀。我们成功地用大鼠的固定应激（IMO）模拟了这种心脏病发作，这是一种众所周知的情绪应激动物模型。联合阻断α-和β-肾上腺素受体的预处理可完全消除imo诱导的心脏变化，提示过度的交感神经-肾上腺髓质流出参与了心脏变化。为了研究这些心脏变化是否在老年女性受试者中尤为突出，我们比较了在接受安慰剂治疗（OVX+P）的去卵巢大鼠和补充b-雌二醇（OVX+E）的去卵巢大鼠对IMO的心功能和心脏或大脑中c-fos mRNA或c-fos免疫反应（IR）的诱导。OVX+P大鼠LVG %收缩率在应激作用下明显降低，而OVX+E大鼠变化不明显。在两组中，心率都因压力而显著增加。然而，应激时OVX+P组的心率明显高于OVX+ e组。OVX+ e - 3对IMO反应的心脏和室旁下丘脑核中c-fos mRNA的表达减弱。OVX+ e - 4组儿茶酚胺能神经纤维的神经支配减少。与之前的研究结果一致，IMO在大鼠大脑皮层、中隔、丘脑、下丘脑、中脑、脑桥和延髓中均观察到c-Fos-IR细胞的增加。OVX+E与OVX+P相比，c-Fos-IR细胞在侧隔、室旁下丘脑核、下丘脑背内侧核、内侧杏仁核、外侧导水渠周围灰质、侧背侧核、被盖核和蓝斑核的数量明显减少，而在室旁丘脑核和孤束核的数量明显增加。这些数据表明，这些区域的神经元活动受到全身雌激素水平的影响。综上所述，雌激素减轻了中枢神经系统和心脏组织的应激反应。反过来，雌激素的减少可能强调绝经后女性应激诱导的Tako-tsubo型心肌病的高发。少

Emotional or physical stress triggers Tako-tsubo cardiomyopathy in postmenopausal female, which is characterized by elevation of ST segment in the ECG and left ventricular apical ballooning in the LVG. We succeeded to mimic this cardiac attack using immobilization stress (IMO) of rats, a well-known animal model of emotional stress. IMO-induced cardiac changes are completely cancelled by pretreatment with combined blockade of α- and β-adrenoceptors, suggesting that exaggerated sympatho-adrenomedullary outflow is involved in the cardiac change. To study whether these cardiac changes are especially predominant in elderly female subjects, we compared cardiac function and the induction of c-fos mRNA or c-Fos- immunoreactive(IR) in the heart or the brain in response to IMO between ovariectomized rats with placebo treatment (OVX+P) and ovariectomized rats supplemented with b-estradiol (OVX+E).1.In OVX+P rats, % contraction in LVG was significantly reduced in response to stress, whole it was n … More ot significantly changed in OVX+E rats. In both groups, heart rate was significantly increased in response to stress. However, heart rate in stress was significantly higher in OVX+P than in OVX+E.2.Expression of c-fos mRNA in the heart and paraventricular hypothalamic nucleus in response to IMO was attenuated in OVX+E.3.Innervation of catechoraminergic nerve fibers was reduced in OVX+E.4.Increased c-Fos-IR cells in response to IMO were observed in cerebral cortex, septum, thalamus, hypothalamus, midbrain, pons and medulla oblongata in accordance with previous findings. In OVX+E compared with OVX+P, the numbers of c-Fos-IR cells were significantly lower in the lateral septum, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, medial amygdaloid nucleus, lateral periaqueductal gray, laterodorsal, tegmental nucleus and locus coeruleus, while they were significantly higher in paraventricular thalamic nucleus and nucleus of the solitary tract. These data suggest that neuronal activity in these areas is influenced by systemic estrogen level.Taken together, estrogen attenuates the stress response in the central nervous system and cardiac tissues. In turn, reduction of estrogen may underline the high incidence of stress-induced Tako-tsubo carrdiomyopathy in postmenoausal female. Less