Wu Wei, Xu Bei, Huang Haibin, Mao Ying, Gao Yuan, Bu Wenhao
Department of Anesthesiology, CR & WISCO General Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, 430080, China.
Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, China.
J Artif Organs. 2025 Jan 6. doi: 10.1007/s10047-024-01488-2.
Using autologous orthotopic liver transplantation (AOLT) model in rats, the effect of lipid reactive oxygen species (L-ROS) inhibitor Ferrostain-1 on ferroptosis signal pathway was observed to determine whether ferroptosis occurred in rat liver injury after cold ischemia-reperfusion (I/R). Thirty-two healthy adult SPF male SD rats, 8 ~ 10 weeks old, weight 240 ~ 260 g, were divided into four groups by the method of random number table (n = 8): sham group, I/R group, I/R + Fer-1 group, I/R + DFO group. In the I/R + Fer-1 group, ferristatin-1(5 mg /kg) was intraperitoneally injected 30 min before surgery; in the I/R + DFO group, DFO 100 mg/kg was injected intraperitoneally 1 h before operation and 12 h after operation. Blood samples were taken from the inferior hepatic vena cava 24 h after reperfusion. After anesthesia, the rats were killed and part of their liver tissue was removed. The pathological changes of liver tissue sections were observed under a high-power microscope, and the liver injury was evaluated. Serum malondialdehyde (MDA) and serum levels of ALT, AST and IL-6 were determined by the ELISA method, Reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), MDA, Fe2 + and superoxide dismutase (SOD) were determined in the liver tissue. Compared with the sham group, the serum levels of the IL-6,MDA, AST and ALT in I/R group were obviously higher (P < 0.05); The levels of MDA and Fe in liver tissue were significantly increased (P < 0.05).The levels of SOD, GSH and GPX4 in liver tissue were decreased. The levels of serum MDA, IL-6, AST, and ALT in the I/R + Fer-1 and I/R + DFO groups were significantly lower than those in the I/R group at 24 h after reperfusion. In the I/R + Fer-1 group, the level of MDA in liver tissue decreased significantly, while the level of SOD, GSH and GPX4 in intestinal tissue increased (P < 0.05). In The I/R + DFO group, the levels of MDA and Fe in liver tissue decreased significantly, while the level of SOD in intestinal tissue increased (P < 0.05). Ferroptosis is involved in pathophysiological process of liver injury after cold ischemia-reperfusion in AOLT rats.
采用大鼠自体原位肝移植（AOLT）模型，观察脂质活性氧（L-ROS）抑制剂Ferrostain-1对铁死亡信号通路的影响，以确定冷缺血再灌注（I/R）后大鼠肝损伤是否发生铁死亡。将32只8至10周龄、体重240至260 g的健康成年SPF级雄性SD大鼠，采用随机数字表法分为四组（n = 8）：假手术组、I/R组、I/R + Fer-1组、I/R + DFO组。I/R + Fer-1组在手术前30分钟腹腔注射Ferrostain-1（5 mg/kg）；I/R + DFO组在手术前1小时及手术后12小时腹腔注射DFO 100 mg/kg。再灌注24小时后，从肝下腔静脉采集血样。麻醉后处死大鼠，取部分肝脏组织。在高倍显微镜下观察肝组织切片的病理变化，并评估肝损伤情况。采用ELISA法测定血清丙二醛（MDA）以及血清ALT、AST和IL-6水平，测定肝组织中还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶4（GPX4）、MDA、Fe2+和超氧化物歧化酶（SOD）水平。与假手术组相比，I/R组血清IL-6、MDA、AST和ALT水平明显升高（P < 0.05）；肝组织中MDA和Fe水平显著升高（P < 0.05），肝组织中SOD、GSH和GPX4水平降低。再灌注24小时后，I/R + Fer-1组和I/R + DFO组血清MDA、IL-6、AST和ALT水平明显低于I/R组。I/R + Fer-1组肝组织中MDA水平显著降低，而肠组织中SOD、GSH和GPX4水平升高（P < 0.05）。I/R + DFO组肝组织中MDA和Fe水平显著降低，而肠组织中SOD水平升高（P < 0.05）。铁死亡参与了AOLT大鼠冷缺血再灌注后肝损伤的病理生理过程。
