盐代谢记忆致细胞功能异常的机制

高盐摄入可导致心血管病、胃癌、骨质疏松、自身免疫性疾病等，其中高盐介导的组织细胞炎症在细胞功能异常中有重要作用，但炎症损伤导致细胞功能异常的特征与机制尚待阐明。肝脏和脂肪是慢性炎症反应的主要器官，我们的前期工作发现，高盐干预可损伤肝细胞的线粒体功能，导致肝脏、脂肪组织和细胞的炎症反应和功能异常，即使脱离高盐环境后炎症反应仍持续存在，体现出显著的“盐代谢记忆”现象。予二甲双胍可以改善高盐介导的肝细胞线粒体功能损伤及消除“盐代谢记忆”现象。为此，我们提出假说，并予证实：高盐导致肝脏、脂肪组织及其细胞线粒体功能障碍，产生“盐代谢记忆”及细胞功能异常，而二甲双胍可修复损伤的线粒体，防止“盐代谢记忆”介导的细胞功能异常。本研究以高盐摄入小鼠和盐敏感大鼠为对象，研究高盐干预对多种组织细胞的作用，及线粒体损伤介导炎症导致细胞功能异常的机制，为防治高盐相关的重大疾病提出新的理念与干预策略。

High-salt intake leads to cardiovascular diseases, gastric cancer, osteoporosis and autoimmune disease et al. High-salt mediated inflammatory injury of tissues and cells play an important role in the cellular dysfunction of these illness, but its characteristic and mechanism of cellular dysfunction are unknown. Liver and adipose tissues are the main organs that cause chronic systemic inflammatory injuries. Our pilot study showed that high-salt intake caused mitochondrial dysfunction in liver cells, and the inflammatory effect both in liver and adipose tissues, furthermore these inflammatory effect remained persistent even removal of high-salt stimulation. We called it the "salt metabolic memory" phenomenon. Metformin improved mitochondrial dysfunction of liver cells mediated by high salt intake and eliminated "salt metabolic memory". Based on our previous study and pilot work, we hypothesized that high-salt intake might lead to mitochondrial dysfunction in liver, adipose tissues, and then cause "salt metabolic memory" and cellular dysfunction. Metformin can repair injury of mtDNA and prevent cellular dysfunction mediated by "salt metabolic memory". We plan to confirm this hypothesis through experimental studies. This proposal proposes a novel concept and intervention strategy for the prevention and treatment of high salt related none communicate diseases.