基于CLARITY技术及CNS-ENS-ICC-SMC通路研究厚朴三物汤调控胃肠动力的作用机制

Houpu Sanwu decoction is maturely used for the treatment of Disorders of gastrointestinal motility diseases (DGIMD) more than a thousand years ago in China. The modern clinical trials and evidence-based medical evidences have amply demonstrated that it is highly effective for the DGIMD. However, the mechanism is still essentially unknown. Our previous studies have found that Houpu Sanwu decoction can change the secretion of gastrointestinal hormones and neurotransmitters, strengthen gastrointestinal myoelectricity activity, and promote gastric emptying and small intestinal propulsion rates. It can be seen that Houpu Sanwu decoction regulate gastrointestinal motility by the network functional unit of enteric nervous system-gastrointestinal Cajal interstitial cells-smooth muscle cells (ENS-ICC-SMC). Recent studies indicated that the central nervous system (CNS), such as hypothalamus and medulla oblongata, has a close relationship with the gastrointestinal motility. A new signal pathway of CNS-ENS-ICC-SMC was established between the CNS and ENS-ICC-SMC by the vagus nerve. In this project, we use the innovative approach of CLARITY technology. We aim to find out the changes of CNS-ENS-ICC-SMC pathway after the DGIMD, establish new theoretical foundations and provide novel study stategies for the DGIMD therapy with Traditional Chinese Medicine.

厚朴三物汤被应用于胃肠动力障碍性疾病（DGIMD）的治疗已有千余年历史，现代临床试验及循证医学证据充分证实了其对DGIMD疗效确切，但其具体作用机制尚未明确。前期研究发现，厚朴三物汤可改变胃肠激素和神经递质分泌、加强肌电活动、促进胃排空和小肠推进率，可能通过影响胃肠神经系统- Cajal 间质细胞-平滑肌细胞（ENS-ICC-SMC）功能单位起到调控胃肠动力的作用。已有研究表明，以下丘脑及延髓为代表的中枢神经系统（CNS）与胃肠动力关系密切，其通过迷走神经与ENS-ICC-SMC功能单位形成网络通路（CNS-ENS-ICC-SMC通路）。本课题创新性应用CLARITY技术，研究胃肠动力障碍发生过程中CNS-ENS-ICC-SMC通路的变化，探讨厚朴三物汤对其调控机制，为中医治疗DGIMD奠定理论基础，为胃肠动力学的研究提供新的思路。

厚朴三物汤被应用于胃肠动力障碍性疾病（DGIMD）的治疗已有千余年历史，现代临床试验及循证医学证据充分证实了其对DGIMD疗效确切，但其具体作用机制尚未明确。本课题首先明确了L-Arg盐溶液制备胃肠动力障碍动物模型的具体方案及“双重”成模机制，探索性发现RAS系统与胃肠动力的密切关系；其次，完成了厚朴三物汤的质控研究，将薄层色谱法(TCL)和高效液相色谱法(HPLC)确定为其质控方法；再次，通过meta分析及动物实验进一步肯定了厚朴三物汤的治疗胃肠动力障碍性疾病的确切疗效；最后完整地构建了CLARITY技术设备并将成功的制备了透明脑及肠管组织，证明了该技术用于胃肠动力方面研究的可行性。