高盐摄入与高血压关系密切，还可独立于血压对靶器官造成损伤。最新研究发现，Necroptosis是一种通过特定基因调控新的细胞程序性死亡模式；肾脏分泌的Renalase能够抑制细胞坏死、保护靶器官损伤。本项目在我们研究发现高盐诱导HK-2细胞Necroptosis发生，导致细胞坏死；而Renalase可以逆转上述改变的基础上，提出“Renalase通过调控Necroptosis抑制高盐诱导盐敏感靶器官损伤”的假设，首先拟采用Dahl盐敏感大鼠、基因敲除小鼠，在动物水平研究Necroptosis在盐敏感靶器官损伤中的作用；进一步探究Renalase对Necroptosis发生的调控作用及其可能的分子机制；最后依托我们收集的盐敏感队列DNA样本，探索Necroptosis相关基因多态性与血压对盐干预反应性的关系。本研究对揭示盐敏感靶器官损伤的分子机制，寻找新的高血压药物靶点具有重要意义。

High-salt intake is significantly associated with hypertension, and it also can cause target organ damage independent of blood pressure elevation. Necroptosis is a newly found type of programmed cell death that is regulated by several specific genes. Renalase that is secreted by the kidneys is reported to inhibit cell necrosis and protects target organs from injury. Through Dahl salt-sensitive rats and an interventional study, we found that high salt could induce necroptosis in HK-2 cells, and thus caused cell necrosis, which could be reversed by recombinant Renalase protein. Herein, we put forward the hypothesis “Renalase protected high-salt induced injury by inhibiting necroptosis in salt-sensitive subjects”. Firstly, using the animal models of Dahl salt-sensitive rats, knockout mice, we investigate the role of necroptosis in target organ injury in salt-sensitive rats. Additionally, we further explore the regulatory effects of Renalase on necroptosis and its possible molecular mechanisms. Finally, the relationship between polymorphisms of necroptosis related genes and blood pressure responses to dietary sodium were assessed based on the DNA samples of the salt-sensitive cohort in the previous study. We believe that this work would be of great significance to uncover the molecular mechanism of target organ damage in salt-sensitive subjects as well as to provide the potential therapeutic targets for hypertension in the future.