Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Province, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Organ Transplantation Technology and Application Engineering, Zhengzhou, Henan, China.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Province, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Organ Transplantation Technology and Application Engineering, Zhengzhou, Henan, China.
Eur J Pharmacol. 2024 Feb 5;964:176224. doi: 10.1016/j.ejphar.2023.176224. Epub 2023 Dec 17.
Liver ischemia/reperfusion (I/R) injury commonly occurs after various liver surgeries. Adelmidrol, an N- palmitoylethanolamide analog, has anti-inflammatory, anti-oxidant, and anti-injury properties. To investigate whether adelmidrol could reduce liver I/R injury, we established a mouse of liver I/R injury and an AML12 cell hypoxia-reoxygenation model to perform experiments using multiple indicators. Serum ALT and AST levels, and H&E staining were used to measure liver damage; MDA content, superoxide dismutase and glutathione activities, and dihydroethidium staining were used to measure oxidative stress; mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, MCP-1, and Ly6G staining were used to measure inflammatory response; and protein expression of Bax, Bcl-2, C-caspase3, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were used to measure apoptosis. The experimental results showed that adelmidrol reduced liver I/R injury. In addition, adelmidrol pretreatment elevated AML12 cell activity and reduced I/R-and H/R-induced apoptosis, inflammatory injury, and oxidative stress. ML385, an inhibitor of nuclear factor erythroid2-related factor 2 (Nrf2), reverses liver I/R injury attenuated by adelmidrol. These results suggest that adelmidrol ameliorates liver I/R injury by activating the Nrf2 signaling pathway.
肝脏缺血再灌注（I/R）损伤常见于各种肝脏手术后。Adelmidrol 是一种 N-棕榈酰乙醇酰胺类似物，具有抗炎、抗氧化和抗损伤作用。为了研究 Adelmidrol 是否可以减轻肝脏 I/R 损伤，我们建立了小鼠肝脏 I/R 损伤模型和 AML12 细胞缺氧再复氧模型，使用多种指标进行实验。通过血清 ALT 和 AST 水平以及 H&E 染色来衡量肝脏损伤；通过 MDA 含量、超氧化物歧化酶和谷胱甘肽活性以及二氢乙啶染色来衡量氧化应激；通过肿瘤坏死因子-α、白细胞介素 (IL)-1β、IL-6、MCP-1 和 Ly6G 染色的 mRNA 表达水平来衡量炎症反应；通过 Bax、Bcl-2、C-caspase3 和末端脱氧核苷酸转移酶介导的 dUTP-生物素 Nick 末端标记染色的蛋白表达来衡量细胞凋亡。实验结果表明 Adelmidrol 可减轻肝脏 I/R 损伤。此外，Adelmidrol 预处理可提高 AML12 细胞活性，并减轻 I/R 和 H/R 诱导的细胞凋亡、炎症损伤和氧化应激。核因子红细胞 2 相关因子 2（Nrf2）的抑制剂 ML385 逆转了 Adelmidrol 减轻的肝脏 I/R 损伤。这些结果表明 Adelmidrol 通过激活 Nrf2 信号通路改善肝脏 I/R 损伤。
