我们课题组十年来采用益气开秘方治疗慢传输型便秘，取得显著临床疗效。前期研究提示该方对慢性传输性便秘肠动力损害恢复与cGMP-PKG作用途径密切相关。小样本预初实验提示肠动力障碍小鼠灌胃给予益气开秘方24h后，肠道平滑肌cGMP含量显著提高，MLCK蛋白表达量在升结肠显著升高而在降结肠部分出现下降趋势，肠道动力显著增强。我们认为益气开秘方影响结肠不同部位MLCK激酶控制肠道平滑肌收缩舒张，可能是慢传输性便秘肠动力调控重要作用机制之一。本项目拟在系统研究益气开秘方体内生物学功能基础上，从结肠平滑肌胞内、胞外两个层面，进一步研究益气开秘方调控PKG-CaMK-MLCK-MLC通路不同时间点和结肠不同部位基因、蛋白表达和磷酸化动态改变，以期明确MLCK通路磷酸化在益气开秘方调控便秘过程中作用机制，为慢传输型便秘发病和益气开秘方调控机制研究提供有说服力的实验数据和新的理论解释。

Our group has been using Yiqi Kaimi Recipe (YQKM) on slow transit constipation (STC) for a decade and have achieved notable curative effect. Early study showed that the therapy on transport constipation chronic intestinal damage power recovery was closely related to cGMP-PKG pathway. Small pilot experiment suggested that the content of intestinal smooth muscle cGMP increased significantly, the expressing quantity of MLCK in the ascending colon increased apparently while downtrend in the descending colon, the intestinal dynamic enhanced significantly. We believed that YQKM affected MLCK on the control of intestinal smooth muscle contraction and relaxation, may be one of the important mechanisms of STC intestinal motility. In order to clarify the mechanism of phosphorylation of the MLCK signal pathway when using YQKM to control constipation, the project intends to study YQKM on the basis of the biological function, from both intracellular and extracellular of the intestine smooth muscle. The study will focus on the regulation of YQKM on PKG-CaMK-MLCK-MLC pathway at different time points, different parts of the intestinal tissue genes, protein expression and phosphorylation of dynamic change, which provides convincing experimental data and new theoretical interpretation for the onset of STC as well as the regulation mechanism of the recipe.