基于RhoA/ROCK信号通路研究枸杞多糖联合运动对NAFLD肠道屏障功能的作用效果与机制研究

非酒精性脂肪肝（NAFLD）是一种高发的慢性肝病。目前针对NAFLD的肠道微生物靶向治疗受到高度重视。前期研究发现枸杞多糖（LBP）和有氧运动（AE）对NAFLD具有保护作用，并均可改善NAFLD大鼠肠道菌群结构。LBP作为一种新型益生元，与AE联合干预对NAFLD叠加作用效果及对肠道微生物的影响机制尚不清楚。本研究拟通过高脂饮食喂养构建NAFLD动物模型，观察LBP、AE以及其联合干预对NAFLD的保护作用。通过测定肠道微生物丰度及多样性、RhoA/ROCK信号通路介导的肠道屏障功能、肝脏TLR4/NF-κB信号通路相关指标，探讨LBP、AE发挥保护作用的机制。并通过随机对照试验验证LBP、AE及联合干预对NAFLD患者的作用效果，进一步阐明LBP、AE可调节肠道微生物及屏障功能，并具有协同作用，进而改善NAFLD肝脏的脂质沉积及内毒素血症，为NAFLD的早期防治提供新的方法和理论依据。

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The current strategy of targeted treatment of gut microbiota for NAFLD has received great attention. The research team found that Lycium Barbarum Polysaccharide (LBP) and aerobic exercise (AE) have protective effects on NAFLD, and preliminary experiments show that both can improve the gut microflora dysbiosis in NAFLD rats. As a new type of prebiotics, the combined effect of LBP and AE on NAFLD and its effect on gut microorganisms are unclear. This study intends to construct a NAFLD animal model by feeding on a high-fat diet, and to observe the protective effects of LBP, AE, and their combined intervention on NAFLD. By measuring the abundance and diversity of gut microflora, the intestinal barrier function mediated by the RhoA / ROCK, and related indicators on the liver TLR4 / NF-κB signaling pathway, the protective effect of LBP and AE will be explored. In addition, a randomized controlled intervention study will be conducted to include NAFLD patients for LBP, AE and combined intervention to verify the synergistic effect of LBP and AE. It is further clarified that LBP and AE may improve liver lipid deposition and endotoxemia in patients with NAFLD by regulating intestinal microflora and barrier functions, and provide new nutrition strategies for the early prevention and treatment of NAFLD.