养阴润肠方促进ICC活性维持治疗STC的机制研究

慢传输型便秘(STC)是临床亟待解决的热点和难点问题。研究表明，Cajal间质细胞(ICC)参与胃肠基本电节律调控和神经递质信号传导，在胃肠动力功能网络中居于核心地位。c-kit是ICC特异标志物，干细胞因子(SCF)与其结合后活化下游信号通路，对ICC发育和表型维持具有重要作用。朱秉宜教授运用养阴润肠方治疗STC，组方独特、疗效确切，前期研究初步显示该方可上调便秘大鼠c-kit mRNA表达，促进ICC活性维持，增强结肠运输功能。本研究拟通过动物实验进一步揭示该方对ICC的活性维持作用及其时效和量效关系，阐明该方治疗STC的作用机制；通过细胞实验探讨该方对SCF/c-kit途径下游的PI3K-AKT，Ras-ERK及JAK-STAT信号通路的影响，诠释该方促进ICC活性维持的内在机制，期待发现STC新的治疗靶标，为研究中药靶向药物提供借鉴。

Slow transit constipation (STC) is a hot and difficult clinic problem at present. Research shows that the interstitial cells of Cajal (ICC) participate in the gastrointestinal basic electrical rhythm control and neurotransmitter signaling， which are the key factor in the basic functions of the gastrointestinal network. The specific marker of ICC is c-kit, which combines with stem cell factor (SCF) to activate the downstream signaling pathways. Their combination plays an important role in maintaining the ICC development and phenotype. Professor Zhu Bingyi used Yang-Yin-Run-Chang method as a remedy for STC. This experience-proved formula of Yang-Yin-Run-Chang has the unique composition, which has been shown efficacy in the early clinical studies. The corresponding basic research has shown that the formula can up-regulate the expression level of c-kit mRNA in constipation rat models, maintain ICC activities, and promote the colonic transit function. This study intends to establish the rat model of STC and clarify the time-effect and dose-effect relationship during the ICC activity maintaining in order to explore the therapeutic mechanism of Yang-Yin-Run-Chang formula on STC. Besides, the changes of PI3K-AKT, Ras-ERK and JAK-STAT signal pathways, which are in the SCF/c-kit pathway downstream, will be observed in the experimental cells treated by Yang-Yin-Run-Chang formula. We are supposed to interpret the internal mechanism of ICC activity maintaining, to find new therapeutic target in STC, and to provide a reference to explore the new targeted drugs for subsequent study of traditional Chinese medicine.