Department of Anesthesiology, Chenzhou First People's Hospital, No.102 Luojiajing, Beihu District, Chenzhou City, 423000, Hunan Province, People's Republic of China.
BMC Anesthesiol. 2024 Jul 25;24(1):251. doi: 10.1186/s12871-024-02641-3.
Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury.
Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway.
Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL's anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats.
RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling.
缺血再灌注（I/R）损伤是肝切除和肝移植后肝损伤的一个主要因素，麻醉剂具有保护器官免受这种损伤的能力。
采用缺氧复氧（H/R）建立体外 I/R 肝细胞损伤模型。用 CCK-8 法、流式细胞仪、LDH 法和 ELISA 法检测肝细胞损伤。然后建立体内 I/R 损伤大鼠模型。用 HE 和 TUNEL 染色评估肝组织损伤。用 Western-blot 评估 MAPK/ERK 通路的激活情况。
瑞马唑仑（RMZL）显著提高了 H/R 诱导的肝细胞损伤模型中细胞的活力，减少了细胞凋亡。RMZL 减少了 H/R 诱导的炎症介质（TNF-α和 IL-6）以及 LDH 水平的释放。我们还发现，RMZL 在体内和体外抑制了 p38 和 ERK1/2 的磷酸化。另一方面，刺激 MAPK/ERK 消除了 RMZL 在 H/R 诱导的肝细胞损伤中的抗炎作用。此外，RMZL 减轻了 I/R 大鼠的肝组织损伤。
RMZL 通过抑制 MAPK/ERK 信号通路预防肝 I/R 损伤。
