College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Key Laboratory of Animals Disease Pathogenesis and Comparative Medicine, Harbin 150030, China.
Molecules. 2022 May 4;27(9):2931. doi: 10.3390/molecules27092931.
Ketamine is an anesthetic drug that is widely used in human and veterinary medicine. In the developmental stage, long-term exposure to ketamine may cause serious side effects. MCC950 and VX765 play protective roles in many disease models by regulating the NLRP3/Caspase-1 pathway. This study aims to explore the potential protective effect of MCC950 and VX765 on ketamine-induced liver injury in neonatal rats and clarify its underlying mechanism. After administration of MCC950 and VX765 in a ketamine-induced liver injury rat model, liver function and inflammatory factors were determined, and immunohistochemistry and western blotting were performed. We found that ketamine caused liver injury in 7-day-old SD rats, decreased liver function indexes, and increased inflammation. MCC950 and VX765 effectively alleviated liver damage and inflammation, and downregulated the expression of proteins such as NLRP3, Caspase-1, and GSDMD-N. In summary, these results indicated that MCC950 and VX765 could have potential protective effects on ketamine-induced liver injury through inhibiting the NLRP3/Caspase-1 pathway.
氯胺酮是一种麻醉药物，广泛应用于人类和兽医医学。在发育阶段，长期暴露于氯胺酮可能会导致严重的副作用。MCC950 和 VX765 通过调节 NLRP3/Caspase-1 通路，在许多疾病模型中发挥保护作用。本研究旨在探讨 MCC950 和 VX765 对新生大鼠氯胺酮诱导肝损伤的潜在保护作用，并阐明其潜在机制。在氯胺酮诱导的肝损伤大鼠模型中给予 MCC950 和 VX765 后，测定肝功能和炎症因子，并进行免疫组化和 Western blot 分析。结果发现，氯胺酮可导致 7 日龄 SD 大鼠肝损伤，降低肝功能指标，增加炎症反应。MCC950 和 VX765 可有效减轻肝损伤和炎症反应，并下调 NLRP3、Caspase-1 和 GSDMD-N 等蛋白的表达。综上所述，这些结果表明，MCC950 和 VX765 通过抑制 NLRP3/Caspase-1 通路，对氯胺酮诱导的肝损伤可能具有潜在的保护作用。
