NHE3通过肾脏和小肠对调节机体钠水代谢、维持机体正常血压和体液平衡具有重要作用。我们利用胃泌素受体CCKBR基因全身敲除小鼠和Dahl盐敏感性高血压大鼠，发现胃泌素通过CCKBR能够抑制肠道上皮NHE3的活性并参与了盐敏感性高血压的调节。由此假设，胃泌素通过小肠上皮细胞膜CCKBR受体激活PI3K及NHERF1等信号分子促进NHE3从细胞膜内吞入胞内而抑制NHE3活性，降低肠道对钠的吸收，抑制盐敏感性高血压的发生发展。本课题拟利用CCKBR肠道上皮细胞特异性敲除小鼠、Dahl盐敏感高血压大鼠，以及自行设计制作的不能被机体吸收而仅作用于肠道内膜上皮的大鼠胃泌素-二氧化硅微粒，同时通过细胞体外实验，并结合高血压盐敏感性人体试验，研究胃泌素通过其受体调节肠道上皮细胞NHE3活性调节机体对钠的吸收，及在盐敏感性高血压发生发展中的作用及其相关机制，为盐敏感性高血压的防治提供新的依据。

NHE3 (Na+/H+ exchanger 3) plays an important role in maintaining normal blood pressure and isohydria through regulating the metabolism of sodium and water via kidney and intestine. We have found that gastrin via CCKBR (Cholecystokinin B receptor) inhibits sodium absorption in intestine to regulate the development of salt-sensitive hypertension, with the study using CCKBR knock out mice and Dahl salt-sensitive hypertensive rats. We hypothesize that gastrin via CCKBR on intestine epithelial cells inhibits NHE3 activity by simulating membrane NHE3 to be translocated to cytosis via PI3K/PKC and NHERF1/ezrin pathway, and so as to inhibit sodium absorption and be involved in the development of salt-sensitive hypertension. In this project, we will conduct In Vivo study by using CCKBR intestine epithelium conditional knock out mice (CCKBR flox/flox;VillinCre) , Dahl salt-sensitive hypertensive rats, and rat gastrin peptide binding with SiO2 which can not be absorbed by intestine and work only on intestine epithelial cells, and In Vitro study by using Caco-2bbe cells and SK-CO15 cells, and human study on salt-sensitivity test in hypertensives, to investigate the role and molecular mechanism of gastrin in the regulation of NHE3 activity in intestine to inhibit sodium absorption and regulate salt-sensitive hypertension development. The findings of this study will provide important references and new strategy for the treatment and prevention of salt-sensitive hypertension.