Tan Wanying, Deng Jiangting, Qi Lingjun, Tan Zhenghuai
Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Sichuan Academy of Chinese Medicine Sciences, Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica, Chengdu, Sichuan, China.
Front Pharmacol. 2025 Apr 28;16:1467950. doi: 10.3389/fphar.2025.1467950. eCollection 2025.
The incidence of nonalcoholic steatohepatitis (NASH) is increasing annually, posing a significant threat to human health. NASH is typified by hepatic steatosis, inflammation, and hepatocellular injury, frequently culminating in fibrosis and cirrhosis. Yet, the precise pathogenesis of NASH remains to be fully elucidated. The hepatic sinusoid, which serves as the fundamental structural and functional unit of the liver, is intricately composed of endothelial cells, Kupffer cells, and hepatic stellate cells. Consequently, the homeostasis of the hepatic sinusoidal microenvironment may exert a pivotal influence on the progression and prognosis of NASH. However, the limitations of current NASH animal models have significantly impeded advancements in understanding the disease's pathogenesis and the development of effective therapeutic interventions. In light of these challenges, this review endeavors to delve deeper into the critical role of hepatic sinusoidal microenvironment homeostasis in the pathogenesis of NASH, critically analyze the commonly employed animal models, and comprehensively summarize the most recent and promising developments in drug research and development. It is anticipated that these efforts will collectively expedite the advancement of the field of NASH research and therapeutic innovation.
非酒精性脂肪性肝炎（NASH）的发病率逐年上升，对人类健康构成重大威胁。NASH的典型特征是肝脂肪变性、炎症和肝细胞损伤，常最终发展为纤维化和肝硬化。然而，NASH的确切发病机制仍有待充分阐明。肝窦作为肝脏的基本结构和功能单位，由内皮细胞、库普弗细胞和肝星状细胞复杂地组成。因此，肝窦微环境的稳态可能对NASH的进展和预后产生关键影响。然而，当前NASH动物模型的局限性严重阻碍了在理解该疾病发病机制和开发有效治疗干预措施方面的进展。鉴于这些挑战，本综述致力于更深入地探讨肝窦微环境稳态在NASH发病机制中的关键作用，批判性地分析常用的动物模型，并全面总结药物研发的最新且有前景的进展。预计这些努力将共同加速NASH研究和治疗创新领域的进展。
