Protective role of N -acetyl- l -tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway

作者：Jianxin Wang, Shuna Yu, Jianguo Li, Huiting Li, Hongxin Jiang, Peilun Xiao, Yitong Pan, Jie Zheng, Yu Li, Jiying Jiang · 发表于：Pharmaceutical Biology · 年份：2019 · DOI：10.1080/13880209.2019.1617750 · 被引用次数：24 · 研究领域：Liver Disease and Transplantation、Organ Transplantation Techniques and Outcomes、Drug-Induced Hepatotoxicity and Protection

Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases.Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms.Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H2O2 with or without 10 µM l-NAT for 6 h.Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H2O2 groups when compared with the controls; however, these levels were significantly decreased after l-NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H2O2 group when compared with the controls, after l-NAT intervention.Conclusions: Our findings indicated that l-NAT ma...