盐敏感性高血压是心脑血管疾病发病及致死的独立高危因素。钠氯离子协同运转蛋白NCC位于肾远曲小管上皮细胞，磷酸化活化，重吸收NaCl增多，导致水钠潴留促进盐敏感性高血压的进展。蛋白激酶SPAK是NCC的关键上游激活因子。前期工作验证一氧化氮NO抑制NCC活化延缓盐敏感性高血压的进展，然而具体机制不明。扩血管活性物质一氧化氮NO，保护血管内皮细胞，主要通过介导蛋白激酶S-亚硝基化广泛参与细胞内信号传导。姜黄素是活血化瘀中药姜黄的有效提取物，化学结构明确，可促进NO合成、抗氧化损伤，保护血管内皮，然而对水钠代谢影响研究较少。考虑姜黄素通过上调NO介导SPAK亚硝基化抑制NCC活化，减轻水钠潴留，延缓盐敏感性高血压进展。在细胞及动物体内进行验证。同时应用Biotin-Switch，Isotope-coded affinity tag等蛋白修饰学检测方法探究NO介导SPAK亚硝基化位点，并敲除验证。

Salt-sensitive hypertension is an independent risk factor for the mortality of cardiovascular and cerebrovascular diseases. The activation of the Na+/Cl- cotransporter (NCC)，located on the renal distal induces sodium retention, finally leading to the progression of salt-sensitive hypertension. Protein kinase SPAK is the key upstream activator of NCC. Previous work clarified that NO inhibits the activation of NCC and alleviates the progression of salt-sensitive hypertension, but the specific mechanism is unclear. NO protects vascular endothelial cells and dilating blood vessels, which is mainly involved in S-nitrosylation post translational modification. Curcumin is an effective extract of turmeric, a traditional Chinese medicine for promoting blood circulation and removing blood stasis. It has a clear chemical structure and promotes NO synthesis and anti-oxidant. We hypothesis that curcumin inhibit NCC activation via NO mediates the nitrosylation of protein kinase SPAK, thereby alleviating sodium-sodium retention and salt-sensitive hypertensio . Biotin-Switch assay, Isotope-coded affinity tag and other protein modification assays will be used in this study to investigate the nitrosylation spot of SPAK, and knocking it out for further verification.