慢性肾衰大鼠盐敏感性的中枢RAS调控机制研究

Chronic renal failure has received extensive attention due to high cost of treatment, hospitalization rate and mortality rate. Chronic renal failure patients are usually salt sensitive; however, there is still a lack of studies concerning central rennin-angiotensin system (RAS) controlled mechanism of the salt sensitivity of rats with chronic renal failure. In this project, based on salt sensitive rats of chronic renal failure as a model, brain nuclear RAS-controlled mechanism of central nervous system of rats with chronic renal failure and salt sensitivity will be studied using techniques and methods of salt feeding, RAS blocking techniques, and immunohistochemistry, Western blot, enzyme-linked immunosorbent assay, radioimmunoassay and real time PCR, etc. The association of amount of salt taken in with key brain nuclei activity and RAS level of rats with chronic renal failure will be comprehensively studied, thus finding regularity of salt amount-depended key brain nuclei activity and its RAS level. The association between key brain nuclei activity and its RAS level of such rats will be explored, thus investigating the association and regularity of key brain nuclei RAS level of rats with chronic renal failure with its salt sensitivity, and further elucidating central RAS regulation of salt sensitivity of rats with chronic renal failure. This will provide new theories for central mechanism of salt sensitivity of chronic renal failure and lay the theoretical and experimental basis for chronic renal failure treatment.

慢性肾衰因其治疗费用昂贵、住院率和死亡率高而受到广泛关注和重视。慢性肾衰患者常伴有盐敏感性，但迄今为止，有关慢性肾衰盐敏感性中枢RAS调控机制的研究仍很缺乏。本项目以具有盐敏感性的慢性肾衰大鼠为模型，通过盐干预和脑部RAS阻断技术，用免疫组织化学、蛋白质印迹、酶联免疫吸附、放射免疫分析和实时荧光定量PCR等方法研究慢性肾衰大鼠脑部关键神经核团的RAS水平及其盐敏感性，阐明慢性肾衰大鼠盐敏感性的中枢RAS调控机制。系统研究盐摄入量与慢性肾衰大鼠脑部关键神经核团活性及其RAS水平的关系，找到盐依赖的此类大鼠脑部关键神经核团活性和其RAS水平的规律性；系统研究此类大鼠脑部关键神经核团活性与其RAS水平的关系与规律性；探索此类大鼠关键神经核团RAS水平与盐敏感性的关系与规律性，阐明慢性肾衰盐敏感性的中枢RAS调控机制，为慢性肾衰盐敏感性中枢调控机制提供新理论，为慢性肾衰的防治奠定理论和实验基础。

慢性肾衰因其治疗费用昂贵、住院率和死亡率高而受到广泛关注和重视。慢性肾衰患者常伴有盐敏感性，但迄今为止，有关慢性肾衰盐敏感性中枢肾素血管紧张素系统（RAS）调控机制的研究仍很缺乏。本项目以具有盐敏感性的5/6肾切除慢性肾衰大鼠为模型，通过不同浓度（0.2% NaCl、0.4% NaCl、4% NaCl）盐干预和脑部RAS、ROS及交感输出阻断技术（脑室分别注射Losartan、Tempol或Clonidine），用免疫组织化学、蛋白质印迹、酶联免疫吸附、放射免疫分析、实时荧光定量PCR和组织学检测等方法研究了慢性肾衰大鼠关键脑区（穹隆下器官、室旁核、终板血管器、视上核、延髓头端腹外侧区）的RAS 、氧化应激、交感活性及其盐敏感性，阐明了慢性肾衰大鼠盐敏感性的中枢调控机制。系统研究了盐摄入量与慢性肾衰大鼠关键脑区活性、RAS、氧化应激及交感神经活性的关系，找到了盐诱导的此类大鼠关键脑区活性、RAS、氧化应激及交感神经活性的规律性；系统研究了此类大鼠关键脑区活性与其RAS、氧化应激及交感神经活性的关系与规律性；探索了此类大鼠关键脑区RAS、氧化应激及交感神经活性与盐敏感性的关系与规律性。阐明了慢性肾衰盐敏感性的中枢RAS 调控机制。在本项目的资助下，目前已在国内外学术期刊发表论文6篇，其中SCI论文5篇（1篇已接收；1篇未标注），包括发表在一区，肾脏病领域排名第一的杂志J Am Soc Nephrol的SCI论文1篇，二区Top Journal的SCI论文2篇。同时，已投稿或修回的SCI论文4篇，还有2篇SCI论文正在准备投稿中；已授权中国发明专利1项。随着本项目的开展，将为慢性肾衰盐敏感性中枢调控机制提供新理论，为慢性肾衰的防治奠定理论和实验基础。对慢性肾脏疾病的认识和防治将起到重要的促进作用，并对慢性肾脏病密切相关的学科产生一定的影响。