基于GAS/CCKBR抑制肠道NHE3活性调节钠吸收探讨温阳益气方治疗慢传输型便秘的作用机制

慢传输型便秘(STC)是临床常见病，严重影响人们生活质量，是目前亟待解决的临床难点问题。钠氢交换体3（NHE3）在肠道钠代谢中有重要作用，抑制肠道NHE3可减少肠道钠吸收而治疗便秘。研究证实胃泌素（GAS）可通过胃泌素B型受体（CCKBR）调节肠道钠代谢，其机制是通过抑制肠道NHE3来实现。温阳益气方临床治疗STC疗效显著，课题组前期发现温阳益气方可提高大鼠粪便含水量，抑制肠道NHE3表达，同时结合网络药理学筛选出温阳益气方君药的核心靶点网络，发现NHE3为其治疗STC的关键靶点。因此提出科学假说：温阳益气方介导GAS/CCKBR抑制肠道NHE3活性抑制钠的吸收，增加肠道内水分而实现其防治STC的作用。本课题拟通过动物和细胞实验探讨温阳益气方干预GAS/CCKBR抑制肠道NHE3活性调节钠吸收治疗STC的具体机制，有助于为中医药治疗STC探寻新的治疗靶点提供实验依据。

Slow transit constipation (STC) is a common clinical disease that seriously affects people's quality of life and is a clinical problem that needs to be solved urgently. Sodium-hydrogen exchanger 3 (NHE3) plays an important role in intestinal sodium metabolism. Inhibiting intestinal NHE3 can reduce intestinal sodium absorption and treat constipation. Studies have confirmed that gastrin (GAS) can regulate intestinal sodium metabolism through the gastrin B-type receptor (CCKBR), and its mechanism is achieved by inhibiting intestinal NHE3.Our previous study demonstrated that Wenyang Yiqi Formula is effective in clinical treatment of STC. The previous work of our research group confirmed that Wenyang Yiqi Formula can increase the fecal water content of rats and inhibit the expression of NHE3 in the intestines, combined with network pharmacology, the core target network of the core drugs of Wenyang Yiqi Formula was screened out, and NHE3 was found to be its key target for the treatment of STC.Therefore, we hypothesized that the mechanism of Wenyang Yiqi Formula in treating STC may be the inhibition of NHE3 activity in the intestine by GAS / CCKBR to inhibit sodium absorption. This study intends to further explore the specific mechanism of Wenyang Yiqi Formula through GAS /CCKBR pathway to inhibit NHE3 activity and then regulate sodium absorption to treat STC through animal and cell experiments. Ultimately, the results of this study will provide experimental basis for finding new therapeutic targets for Chinese medicine treatment of STC.