非酒精性脂肪性肝炎（NASH）是全球公共卫生问题，可能会进展为纤维化、肝硬化和肝癌，并且治疗选项有限。尽管核苷酸结合寡聚化结构域样受体家族丝裂原活化因子域蛋白3（NLRP3）炎症小体与NASH进展密切相关，烟酸（NA）作为一种治疗血脂异常的维生素，是一种新兴的治疗肝脂肪变性和纤维化的药物。在本研究中，我们调查了NA对实验性NASH的药理作用，并探讨了NLRP3炎症小体/焦亡反应抑制是否是其行动机制之一。将大鼠喂食高脂高糖饮食，添加胆固醇和低剂量的CCl4。NA显著减少了炎症反应，降低了肿瘤坏死因子-α和核因子κB的蛋白水平。此外，NA抑制了NLRP3-凋亡相似蛋白中含有卡斯珀招募结构域-Caspase-1的复合物的形成，降低了白细胞介素-1β、白细胞介素-18和气孔形成素D的蛋白水平。此外，NA还降低了肿瘤生长因子-β、α-平滑肌肌动蛋白以及胶原-1的肝脏水平，因此降低了细胞外基质合成。我们的结果表明，NA可以抑制NASH的进展，并鼓励进一步进行关于NA在治疗人类NASH方面的基础和临床研究。版权所有 © 2023年。Elsevier Inc.出版。

Non-alcoholic steatohepatitis (NASH) is a global public health concern that may progress into fibrosis, cirrhosis, and liver cancer, with limited curative treatment options. While the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is closely linked to NASH progression, nicotinic acid (NA), a vitamin used for the treatment of dyslipidemia, is an emerging pharmaceutical treatment for hepatic steatosis and fibrosis. Here, we investigated pharmacological effects of NA on experimental NASH and whether NLRP3 inflammasome/pyroptosis inhibition is an associated mechanism of action. Rats were fed a high-fat sucrose diet supplemented with cholesterol and a low dose of CCl4. NA significantly reduced inflammation by decreasing the protein levels of tumor necrosis factor-alpha and nuclear factor kappa B. Moreover, NA inhibited the formation of NLRP3- apoptosis-associated speck-like protein containing caspase recruitment domain-Caspase-1, decreasing interleukin-1beta, interleukin-18, and gasdermin D protein. In addition, NA reduced tumor growth factor-beta, alpha-smooth muscle actin, and hepatic levels of collagen-1, consequently decreasing extracellular matrix synthesis. Our results indicate that NA can inhibit NASH progression and encourage further basic and clinical studies on the use of NA for the treatment of human NASH.Copyright © 2023. Published by Elsevier Inc.