肾上腺素和去甲肾上腺素对小鼠肝脏hepcidin表达的调控机制研究

With the accelerated pace and increased pressure of daily life, more and more people are suffering from hepertension. It has been reported that the levels of adrenaline and norepinephrine increased significantly in hypertension patients, and the serum iron level also increased. But it was still unclear whether adrenaline and norepinephrine regulate the iron metabolism in the body. Our previous study have shown that adrenaline and norepinephrine can up-regulate the hepcidin expression. In this proposal, we study the signal pathway and related receptors in the regulation of adrenaline and norepinephrine on hepcidin, and the impact on the iron levels in organs. This will provide some insight into the relationship of hepytension and abnormal iron metabolism.

随着生活节奏的加快，工作压力的增大，患高血压的人数越来越多。研究证实高血压患者血清中肾上腺素和去甲肾上腺素的水平明显增高，血清铁也增加明显。肾上腺素和去甲肾上腺素对机体铁代谢是否有调控作用，目前尚未有足够研究。本研究在已有肾上腺素和去甲肾上腺素上调hepcidin表达的基础上，进一步研究肾上腺素和去甲肾上腺素对hepcidin表达调控的受体途径和信号通路，通过对各器官铁水平变化的测定，为全面认识铁代谢与高血压形成的关系提供有益的证据。

血清中肾上腺素和去甲肾上腺素的与高血压的发病具有重要的相关性，然而，其发病机制尚不完全明了。本研究在已有肾上腺素（AD）和去甲肾上腺素（NE）上调hepcidin表达的基础上，进一步研究了肾上腺素和去甲肾上腺素对hepcidin表达调控的受体途径和信号通路，研究发现AD、NE通过α型肾上腺素能受体及其下游信号分子STAT3的磷酸化信号通路，作用小鼠肝脏hepcidin的启动子，进而引起hepcidin 表达增加。AD、NE连续处理小鼠7天后，能够引起血清铁升高，血管周围和脾脏铁积累，这一积累与hepcidin引起的FPN1表达下降有密切关系。本实验首次研究肾上腺素和去甲肾上腺素与铁调素之间的关系，发现了STAT3的磷酸化的信号通路参与了AD、NE对 hepcidin的调节。这些研究为更全面的了解关于高血压与铁之间关系的研究提供了一个新思路。