基于脾藏意理论的呆病名方经P-gp途径调节肠脑之间炎症免疫通信紊乱的益智机制

近年来最重要的科学发现之一是肠道微生态参与肠脑之间的双向通信。研究表明，老年性痴呆(AD)脑破坏机制始于肠道微生态失调、炎症发展及肠脑通信调节紊乱，这与中医对呆病“始于肝气之郁,终于胃气之衰”的病机观点不谋而合。在前期国科金项目中，我们发现名方洗心汤能保护Aβ/tau毒性引起的神经损伤，并通过调控记忆关键通路发挥益智作用。然而，通过色谱方法我们也发现，洗心汤标志性成份中仅有少量直接进入血脑屏障，这与全方药物效应形成较大反差。因此，作为从脾胃论治的复方，洗心汤可能经肠道起始途径影响肠脑双向通信的网络调控新机制，留给我们令人兴奋的期待。本研究采用HPLC-FLD及分子生物学等方法，观察洗心汤通过抗炎性P-gp途径干预肠道微生态失调及菌群衍生物透肠入脑引发炎症免疫通信紊乱的分子效应。研究将揭示名方经肠道内化代谢方式调节肠脑通信紊乱的益智机制，诠释“脾藏意主思”的科学内涵，为AD防治提供坚实依据。

One of the most important scientific discoveries in recent years is that intestinal microecology is involved in two-way communication between the gut and brain. Studies have shown that the brain damage mechanism of alzheimer’s disease (AD) is the imbalance of intestinal microecology, the development of inflammation and the regulation of intestinal and brain communication. This happens to coincide with the idea of “AD beginning depression of liver qi and finishing failure of stomach qi”. In the earlier project, we found that Xixin decoction can protect the damage caused by Aβ/tau toxicity, and play a nootropic role in regulating the key memory pathways. However, we also found by HPLC method that only a small amount of the signature ingredients of Xixin decoction directly entered the blood-brain barrier, which was in great contrast to the drug effect of this prescription.Therefore, as a famous prescription on the treatment of AD from spleen and stomach, Xixin decoction began regulating from intestine and had an impact on regulatory mechanism of two-way communication network between intestine and brain, which gave an exciting expectation. In this study, HPLC-FLD and molecular biology methods were used to observe the effects of Xixin decoction on intestinal microecology intervention through anti-inflammatory p-glycoprotein pathway and main products of microbiota penetrating the intestine into the brain to induce inflammatory immune communication disorder. The study will discover the nootropic mechanism of Xixin decoction by enteric metabolism regulating entero-brain communication network and interpret a scientific connotation for spleen storing idea and governing thought as to provide a scientific basis for preventing and treating AD.