中文摘要
“主运化”和“升清阳”是脾的两大基本功能,脾虚泄泻常伴随着脾失运化所致的营养物质吸收障碍。补中益气汤治疗脾虚泄泻有显著的疗效。钠依赖葡萄糖转运体1(SGLT1)是葡萄糖经小肠吸收的主要载体,钠-氢交换体3(NHE3)的活性状态与泄泻发生密切相关,而SGLT1是启动NHE3转位至小肠刷状缘上的关键因素,该过程的发生需要p38MAPK/Akt2信号转导途径的介导。补中益气汤可提高小肠粘膜SGLT1的表达。推论该方治疗脾虚泄泻与其调控SGLT1经p38MAPK/Akt2信号转导途径介导NHE3表达有关。项目拟从动物水平观察脾虚证及予补中益气汤干预前后葡萄糖吸收及相关物质的变化,并在细胞水平上对SGLT1与NHE3之间的关联性进行验证,采用siRNA技术,在基因、蛋白水平探讨SGLT1对NHE3调控的分子机制及补中益气汤的干预效果,为探明脾失运化所致泄泻的科学本质及益气升阳法的作用机理提供依据。
英文摘要
“Governing transportation and transformation” and “ascending lucid Yang” are two basic physiological function of spleen. Diarrhea due to spleen deficiency is often associated with nutrient absorption barriers caused by the spleen’s failure in transportation and transformation. Bu-zhong-yi-qi Tang (BZYQT) is common used as a “tonifing Qi and raising Yang” formula in Chinese Medicine and has significant effect of treating diarrhea due to spleen deficiency. SGLT1 is the main carrier of glucose by the small intestine absorption. NHE3 activity status and diarrhea is closely related. SGLT1 is the key factor to start NHE3 transposition to the intestinal brush border, and this process requires p38MAPK/Akt2 signal transduction pathway mediated. Bu-zhong-yi-qi decoction can increase the expression of SGLT1 in the mucous membrane of small intestine . So we propose that BZYQT in the treatment of diarrhea due to spleen deficiency is related to mediating the expression of NHE3 by regulating SGLT1 by p38MAPK/Akt2 signal transduction pathway. This subject intends to observe the changes of glucose absorption capacity and related substances of spleen deficiency syndrome and before and after BZYQT intervention from animal level. The correlation between SGLT1 and NHE3 will be verified at the cellular level. The molecular mechanism of SGLT1 regulating NHE3 and interfering effects of BZYQT will be explored from different levels of genes and protein by using siRNA technology too. In all, this project will illustrate the physiologic behaviors of diarrhea due to spleen deficiency, and provide the basis for the mechanism of “tonifing Qi and raising Yang”.
