基于钠水潴留致肾病综合征水肿发生进程及机制研究当归芍药散活血利水的科学内涵

水肿是肾病综合征主要临床表现，钠水潴留及血容量的改变是水肿发生的主要因素。临床及基础研究表明当归芍药散治疗肾病综合征水肿确有疗效，但机理并不清晰。本课题组认为肾病综合征水肿进程中存在钠水潴留的不同机制，提出当归芍药散及其配伍（活血药组和利水药组）同时干预肾病综合征水肿发生进程（钠水潴留阶段、钠代偿阶段和单纯性水液潴留阶段）而发挥整合调节作用的假说。首先在不同时间点动态观察肾病综合征模型大鼠钠转运蛋白和体液成分变化，揭示水肿发生进程；然后采用蛋白印迹、免疫荧光、生物电阻抗等多种技术手段检测纤溶酶介导γ-ENaC的裂解激活、NO介导NKCC2代偿性降低和AVP/AngⅡ促进AQP2穿梭的交互作用机制，并研究当归芍药散及配伍组的干预作用。本课题有望从肾病综合征水肿发生进程的钠水潴留关系揭示当归芍药散活血利水作用机制，进一步阐明当归芍药散活血利水的科学内涵。

Edema is the classic clinical presentation of the nephritic syndrome. Changes of blood volume, sodium and water retention are the major cause of edema. Clinical and basic research shows that Danggui Shaoyao San(DSS), a famous Chinese formula for invigorating blood and promoting diuresis, has a definite effect in treating nephrotic edema, but the mechanism of treatment and the scientific connotation of the prescription are still unclear. With the further understanding of the disease, this project suggests that there are different mechanisms of sodium and water retention in the process of nephrotic edema, and propose that the process of nephrotic edema includes sodium retaining stage (follow by water retention), sodium compensatory stage and the final stage of water retention, and the blood-associated herbs group and water-associated herbs group in DSS simultaneous intervention in edema process to play an integrated role. Firstly, the changes of sodium transporter, body composition and fluid status in rats with nephrotic syndrome were observed dynamically at different time to reveal the process of edema. Then, many techniques such as western blot, immunofluorescence, fluorescence microscopy, patch clamp and bioelectrical impedance were used to detect the proteolytic activation ofγ-ENaC by urinary serine protease plasmin, NO mediated NKCC2 compensatory reduction, and the crosstalk between vasopressin and angiotensin II on apical targeting of AQP2. The regulating effect of DSS and its decomposition group were also studied. Based on the progress of edema in nephrotic syndrome induced by sodium and water retention, this study investigated the regulating effect of DSS on different stages of sodium and water retention. It is expected to further elucidate the mechanism of DSS in invigorating blood and promoting diuresis and reveal the scientific connotation of DSS.