心肌缺血后伤害性刺激传入中枢兴奋交感传出神经，加重心肌损伤。我们前期研究表明侧脑室给予阿片能减轻心肌缺血后损伤，但中枢阿片介导心肌保护作用的确切机制仍不清楚。下丘脑室旁核（PVN）和头端延髓腹外侧区（RVLM）与心脏交感传出神经存在联系，我们进一步证实PVN和RVLM之间为一级突触联系，同时RVLM注射吗啡能减轻心肌缺血后损伤，并且降低orexin的表达。由此我们推测通过orexin受体调控PVN-RVLM神经环路可能是中枢阿片减轻心肌缺血后损伤的机制之一。为证实这一假说，本研究拟用转基因小鼠建立心肌缺血后损伤模型，应用神经示踪、透明脑、光遗传、电生理、钙离子成像等技术，探究PVN-RVLM神经环路如何参与调控心肌缺血后伤害性信号及中枢阿片通过orexin受体调控该环路的机制。本课题将阐明中枢阿片减轻心肌缺血后伤害性刺激的神经机制，为心肌缺血后损伤的防治提供新靶点。

Myocardial ischemia injury stimulates sympathetic efferent fibers relaying a signal to the nociceptive center in the brain. Activation of such neuronal circuits further aggravates myocardial injury. Our previous studies have demonstrated that opioids administration to the lateral ventricle can alleviate myocardial ischemic injury, however, the role and mechanism of central opioids involving in myocardial protection are still unclear. There is evidence for a neural connection between hypothalamus paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM), and the cardiac sympathetic efferent fibers. Consistent with this, our pervious study revealed a first-order connection between PVN and RVLM. In addition, we showed that morphine injection into RVLM reduced myocardial ischemic injury and the expression of orexin receptor. In the light of these findings, we speculate that opioid regulation of the PVN-RVLM nerve circuits through orexin receptors might be one of the mechanisms to alleviate nociceptive stimulation after myocardial ischemia. We will test this hypothesis in an animal model with myocardial ischemia injury using various technical approaches. These approaches include neural tract tracing, transparent brain, optogenetics, electrophysiology and calcium real-time imaging techniques in transgenic mice. This investigation should provide a novel mechanism and a therapeutic target by which central opioid acts its antinociceptive action in the treatment of myocardial ischemia.