交感神经系统在心血管活动的调控中起重要作用，是维持机体稳态的重要组成部分。交感神经功能亢进参与了如慢性心力衰竭（CHF）等心血管疾病的发生和发展。神经体液因素可引起CHF中枢交感输出的亢进，但外周体液因素对中枢交感输出的调控机制尚未完全阐明。外泌体作为体液因素中可以自由进出血脑屏障的因子，是否参与了CHF的心脑交互对话从而导致中枢交感输出增强尚不清楚。因此，本项目的总体目标是明确循环外泌体在CHF中枢交感输出亢进中的作用和意义。在CHF模型和神经细胞层面，将明确：1）循环外泌体对中枢交感输出的作用；2）外泌体源性的miR-16-5p在CHF中枢交感亢进中的作用；3）交感中枢内miR-16-5p调节Ntrk2-PI3K-Akt通路在神经炎症反应中作用。以上研究将为阐明CHF状态下心脑交互对话的非神经反射机制提供重要的理论依据，为探索CHF的发生机制和防治策略提供新的方向。

Sympathetic nervous system plays an important role in the regulation of cardiovascular activities as well as maintaining the homeostasis of the body. Overactivation of sympathetic nervous system is involved in the physiopathologic mechanism of cardiovascular diseases such as chronic heart failure (CHF). Hyperactivity of sympathetic outflow under CHF is mainly mediated by nervous and humoral regulation, however, the regulatory mechanism of peripheral humoral factors on central sympathetic outflow under CHF is still unclear. The exosome, as a humoral factor that can go through the blood-brain barrier freely, arouses our interest as to whether it participates in the interaction between the heart and the brain in the process of CHF and thus leads to the enhancement of central sympathetic outflow. Therefore, the overall objective of this project is to clarify what roles circulatory exosomes of rats with CHF play in the overactivity of central sympathetic outflow. Using rats with CHF and PC12 nerve cells, we hope to ascertain: 1) the effect of exosomes on central sympathetic outflow; 2) the role of exosome-derived miR-16-5p in central sympathetic overactivity under CHF; 3) the regulatory mechanism of miR-16-5p/Ntrk2/PI3K/Akt axis on neuro-inflammatory response in sympathetic center. The data from this project will contribute to clarifying the non-neural reflex mechanism of the interaction between heart and brain in CHF, which might provide a new direction and basis for the exploration of the pathogenesis, prevention and treatment strategies of CHF.