肝细胞癌（HCC）仍然是全世界最常见的肝癌类型。二乙基亚硝胺（DEN）诱导的肝癌是实验动物中广泛使用的肝癌模型。乙酰唑酰胺 (AZA) 是一种碳酸酐酶抑制剂。本研究旨在评估 AZA 对 DEN 诱导的 HCC 的治疗机制。将三十只雄性 Wistar 白化大鼠平均分为三组。第 I 组 (C)：对照组，第 II 组 (HCC)：DEN 诱导的 HCC，第 III 组 (HCC/AZA)：AZA 治疗的 HCC。肝酶活性升高、甲胎蛋白 (AFP) 水平升高以及明显的肝脏结构变化证实了 DEN 诱导的 HCC。另一方面，AZA 治疗的 HCC 组血清肝酶活性和 AFP 水平降低，肝脏结构受到调节。此外，它还下调 p-p38 MAPK/p-JNK1/JNK2/p-C-Jun/p-NF-κB p65 蛋白表达。此外，它还通过控制 p-AMPK/p-mTOR1/LC3 I/II 蛋白的表达来改善自噬。此外，它还下调碳酸酐酶-IX (CAIX) 和己糖激酶-II (HKII) 的相对基因表达。 AZA 处理的 HCC 肝组织的组织病理学检查支持了这些发现。结论：AZA 通过改善 CAIX 和 HKII 基因表达介导的肝脏生物标志物、抗氧化状态、炎症标志物和自噬的调节，为改善实验诱导的 HCC 提供了一个新的维度。© 2024 Société Française de Pharmacologie et de Thérapeutique。约翰·威利出版

Hepatocellular carcinoma (HCC) continues to be the most prevalent type of liver cancer worldwide. Diethylnitrosamine (DEN)-induced HCC is an extensively used hepatic cancer model in experimental animals. Acetazolamide (AZA) is a carbonic anhydrase enzyme inhibitor. This study aimed to assess the therapeutic mechanism of AZA against DEN-induced HCC. Thirty male Wistar albino rats were divided equally into three groups. Group I (C): control group, Group II (HCC): DEN-induced HCC, and Group III (HCC/AZA): AZA-treated HCC. Verification of the HCC induced by DEN was confirmed by elevated liver enzymes' activities, and increased α-fetoprotein (AFP) levels, as well as distinct liver architecture changes. On the other hand, the AZA-treated HCC group experienced decreases in the activities of serum liver enzymes and AFP levels, as well as, regulated liver architecture. Additionally, it downregulated p-p38 MAPK/p-JNK1/JNK2/p-C-Jun/p-NF-κB p65 protein expressions. Moreover, it ameliorated autophagy by controlling the expression of the p-AMPK/p-mTOR1/LC3 I/II proteins. Furthermore, it downregulated the relative gene expressions of carbonic anhydrase-IX (CAIX) and hexokinase-II (HKII). Histopathological examination of AZA-treated HCC liver tissues supported these findings. Conclusion: AZA provides a new dimension in ameliorating experimentally induced HCC through regulation of hepatic biomarkers, antioxidant status, inflammatory markers, and autophagy, mediated by amelioration of CAIX and HKII gene expressions.© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.