- 作者：Ge Zhao ; Hongwei Ma ; Xin Shen ; Gao-Feng Xu ; Yu-Lin Zhu ; Baoying Chen ; Ru Tie ; Ping Qu ; Yi Lv ; Haifeng Zhang ; Jun Yu
- 关键词：Propofol ; Ischemia-reperfusion injury ; Liver ; Glycogen synthase kinase 3尾 ; Mitochondrial permeability transition pore ; Apoptosis
- 刊名：Journal of Surgical Research
- 出版年：November, 2013
- 年：2013
- 卷：185
- 期：1
- 页码：388-398
- 全文大小：2063 K
Background
It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3尾 (GSK-3尾) is known to play an important role in the oxidative stress-induced apoptosis. In this study, we investigated the role of GSK-3尾 and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury.Materials and methods
The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90聽min, respectively. Reperfusion of 120聽min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential.
Results
Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Importantly, propofol suppressed the mitochondrial GSK-3尾 by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse.
Conclusions
Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3尾.