Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Gut Microbes. 2021 Jan-Dec;13(1):1972746. doi: 10.1080/19490976.2021.1972746.
Activation of the NOX4/NLRP3 inflammasome pathway has been associated with fibrosis in other organs. An imbalance in intestinal bacteria is an important driving factor of liver fibrosis through the liver-gut axis. This study aimed to explore whether the effect of ursolic acid (UA) on liver fibrosis was associated with the NOX4/NLRP3 inflammasome pathways and intestinal bacteria. Wild-type (WT), , and mice and AP-treated mice were injected with CCI4 and treated with or without UA. The intestinal contents of the mice were collected and analyzed by 16S rRNA sequencing. UA alleviated liver fibrosis, which manifested as decreases in collagen deposition, liver injury, and the expression of fibrosis-related factors, and the expression of NOX4 and NLRP3 was significantly inhibited by UA treatment. Even after CCI4 injection, liver damage and fibrosis-related factors were significantly decreased in , and AP-treated mice. Importantly, the expression of NLRP3 was obviously inhibited in and AP-treated mice. In addition, the diversity of intestinal bacteria and the abundance of probiotics in and mice was significantly higher than those in WT mice, while the abundance of harmful bacteria in and mice was significantly lower than that in WT mice. The NOX4/NLRP3 inflammasome pathway plays a crucial role in liver fibrosis and is closely associated with the beneficial effect of UA. The mechanism by which the NOX4/NLRP3 inflammasome pathway is involved in liver fibrosis may be associated with disordered intestinal bacteria.
NOX4/NLRP3 炎性小体通路的激活与其他器官的纤维化有关。肠道细菌失衡是通过肝肠轴导致肝纤维化的一个重要驱动因素。本研究旨在探讨熊果酸 (UA) 对肝纤维化的作用是否与 NOX4/NLRP3 炎性小体通路和肠道细菌有关。野生型 (WT)、 和 小鼠和 AP 处理的小鼠注射 CCI4 并分别用或不用 UA 处理。收集小鼠的肠道内容物并通过 16S rRNA 测序进行分析。UA 减轻了肝纤维化，表现为胶原沉积、肝损伤和纤维化相关因子的表达减少，UA 处理显著抑制了 NOX4 和 NLRP3 的表达。即使在 CCI4 注射后， 小鼠和 AP 处理的小鼠的肝损伤和纤维化相关因子明显减少。重要的是， 和 AP 处理的小鼠中 NLRP3 的表达明显受到抑制。此外， 和 小鼠的肠道细菌多样性和益生菌丰度明显高于 WT 小鼠，而 和 小鼠的有害细菌丰度明显低于 WT 小鼠。NOX4/NLRP3 炎性小体通路在肝纤维化中起关键作用，与 UA 的有益作用密切相关。NOX4/NLRP3 炎性小体通路参与肝纤维化的机制可能与肠道细菌紊乱有关。
