乳糖不耐受引起的慢性腹泻日益增多并受到重视,但对肠腔生态系统影响及机制并不清楚。健脾中药具有显著止泻作用但靶点不明确。通过改良高乳糖腹泻脾虚证模型模拟乳糖不耐受脾虚证发现：梯度增加高乳糖浓度可以维持大鼠慢性腹泻状态，肠内容物短链脂肪酸（short chain fatty acid, SCFA）含量明显降低。参苓白术散灌胃后症状改善且逆转SCFA含量。推测菌群失调引起肠腔内SCFA变化，继而肠上皮Na+和Cl-转运失调是主要病理机制，可能是参苓白术散作用靶点。本项目使用参苓白术散干预改良高乳糖腹泻脾虚证正常和无菌动物模型;利用高通量测序检测模型鼠及干预后肠内容物菌群结构；气相及液质联用检测肠内和血SCFA、乳糖及乳酸含量；短路电流及分子生物学方法研究Na+、Cl-转运及信号机制，检测相关通道和SCFA转运体表达和膜转运。期望可以揭示高乳糖腹泻脾虚证肠腔内环境紊乱机制和参苓白术散主要作用靶点。

At present, chronic diarrhea caused by lactose intolerance (LI) is increasing in China, which has been paid more and more attention. However, the effect and mechanism of LI on intestinal ecosystem are not clear. Traditional Chinese medicine for invigorating spleen has significant antidiarrheal effect, but the target is not clear. Earlier experiments through modified spleen deficiency syndrome model with high lactose diarrhea (SD-HLD) found: Gradient increase of high lactose concentration quickly induces and maintains diarrhea to simulate spleen deficiency syndrome lactose intolerance induced chronic diarrhea in rats, the concentration of short chain fatty acid (SCFA) in intestinal contents decreased significantly. The symptoms of diarrhea were significantly improved and the content of SCFA was reversed after intragastric administration of Shenling Baizhu San. We hypothesized that the change of SCFA caused by dysbiosis, followed by the disorder of Na + and Cl - transport in intestinal epithelium, is main pathophysiological mechanism of lactose-induced chronic diarrhea, which may be the target of Shenling Baizhu San. In this project, Shenling Baizhu San was used to improve SD-HLD normal and sterile animals. High-throughput sequencing was used to detect the flora structure of model mice and GC-HPLC-MS was used to the changes of SCFA, lactose and lactic acid content after intervention in the intestinal contents and blood; short-circuit current and molecular biology were used to study the Na+, Cl-transport and signal mechanism of intestinal epithelium, and to detect the expression and trafficking of related channels and SCFA transporters and membrane transport. It is hoped that this study can elucidate the mechanism of intestinal internal environment disorder in high lactose diarrhea with spleen deficiency syndrome and the main target of Shenling Baizhu San.