临床上，患者的交感/肾上腺素受体系统有急性短暂和慢性持续激活状态。两种状态都可导致或加重心脏损害和病理重塑，心脏纤维化是其中的主要病理过程。我们的前期研究结果显示这两种激动模式都可导致心脏纤维化，但纤维化的病理过程有明显差别；心肌巨噬细胞浸润是急性交感激活导致纤维化的关键环节，而慢性纤维化则没有炎症细胞浸润，提示其病理机制不同。因此，本项目拟对交感/肾上腺素受体急性和慢性激动引起心脏纤维化的特点及发生机制进行研究。明确炎性反应是急性交感激活引起心脏纤维化的始动因素及其机制；明确TGF-β等关键促纤维化因子在慢性交感激活引起心脏纤维化中的作用及其机制；探讨肾上腺素受体与TGF-β受体的交互作用；探讨细胞间膜纳米管介导的细胞-细胞相互作用在上述两种纤维化过程中的作用。从而阐明交感/肾上腺素受体激活引起心脏纤维化的启动机制和关键环节，为寻找心脏纤维化更特异干预靶点提供线索和理论基础。

Both acute and chronic activation of sympathetic/adrenergic system are observed in patients in clinical practice. These two patterns of activation can cause or aggravate the pathological remodeling and injury of heart, with cardiac fibrosis as the main pathological changes. Our previous researches revealed that both acute and chronic activation resulted in cardiac fibrosis, but with distinctive pathological processes. The infiltration of macrophages in heart tissue may be pivotal in the acute sympathetic activation induced cardiac fibrosis, while no inflammatory cell was found in the chronic mode of fibrosis, which suggests the different underlying pathological mechanisms. Thus this research project is to study the features and onset mechanisms of cardiac fibrosis caused by both acute and chronic activation of sympathetic/adrenergic system. The processes and mechanisms will be investigated to illuminate the initiating role of inflammatory responses in the acute cardiac fibrosis, the role of key pro-inflammatory factors, including TGF-β, in the chronic cardiac fibrosis, the interaction of adrenergic receptor and TGF-β receptor signaling pathways, and the role of nanotube mediated intercellular interaction in both patterns of cardiac fibrosis. The onset mechanism and core molecules can thereby be clarified in the cardiac fibrosis induced by adrenergic activation, providing clues and theory basis for develop more specific treating target for cardiac fibrosis.