王氏保赤丸通过B.pseudolongum PV8-2代谢产物拮抗ALD脂质沉积的作用机制研究

酒精性肝病(ALD)是世界上最常见的慢性肝病之一，临床尚无特效药。研究表明，肠道益生菌及其代谢产物影响了肝脏脂质代谢，可作为ALD治疗的新靶点，这与中医“肝病肠治” 的理念相通，但却缺乏相应药物。王氏保赤丸（WBP）是国家配方保密品种，临床常用于胃肠道疾病治疗。我们前期研究发现WBP可有效预防ALD肝脏脂质沉积，减轻氧化应激，加速酒精代谢。进一步研究发现，WBP可以显著升高肠道内源益生菌株假长双歧杆菌PV8-2(BP PV8-2)丰度，改善菌群代谢。该结果提示，WBP可能通过调节肠道益生菌预防ALD肝脏脂质沉积。鉴于前期研究表明，肠道益生菌代谢产物是调节肝脏脂质代谢的关键因素，本项目拟通过体外培养结合三代测序技术、非靶向代谢组等技术，筛选WBP调控的BP PV8-2的关键代谢物，进一步阐明其调节肝脏脂质代谢的关键信号通路。该研究将为WBP调节肠道益生菌缓解ALD机制提供新证据。

Alcoholic liver disease (ALD) is one of the most common chronic liver diseases in the world without specific drug in clinic. Recent studies have shown that intestinal probiotics and their metabolites can affect liver lipid metabolism, which can be used as a new target for the treatment of ALD. This coincides with the concept of "Treating liver via intestine" in traditional Chinese medicine, but lacking of corresponding drugs. Wang Shi Bao Chi Pill (WBP), as a national formula confidential drugs, regularly used in the treatment of gastrointestinal diseases. Our previous study found that WBP can effectively prevent lipid deposition in liver of ALD, reduce oxidative stress and accelerate alcohol metabolism. Further studies showed that WBP could significantly increase the abundance of Bifidobacterium pseudolongum PV8-2 (BP PV8-2) and reduce the level of intestinal inflammation. These results suggest that WBP may prevent liver lipid deposition in ALD by regulating intestinal probiotics. Previous studies have shown that intestinal probiotic metabolites are the key factors in regulating liver lipid metabolism. In this project, BP PV8-2 was cultured in vitro, combined with the single molecule sequencing and non-targeted metabonomics technology, to screen the key metabolites of BP PV8-2 regulated by WBP, and further elucidating the key signal pathway of regulating liver lipid metabolism. This study will provide a new theoretical basis for elucidating the molecular mechanism of WBP regulating intestinal flora to alleviate ALD.