Abstract:

Objective To explore the improvement effect of propofol postconditioning on neurological function in the rats with cerebral ischemia-reperfusion injury and its protective effect on brain mitochondrial injury，and to clarify its mechanism. Methods Twenty-four SD rats were randomly divided into sham operation group， model group and propofol postconditioning group， with 8 rats in each group. The rats in model group and propofol postconditioning group were used to establish the focal middle cerebral artery obstruction focal cerebral ischemia-reperfusion models by carotid artery ligation. The rats in propofol postconditioning group were infused with 20 mg·kg^－1·h^－1 propofol for 2 h in the femoral vein immediately after reperfusion； the rats in sham operation group and model group were given the same amount of normal saline.The neurological deficit scoring in the rats in various groups 24 h after reperfusion were performed； HE staining method was used to observe the pathomorphology of the hippocampus tissue of the rats in various groups； the activities and levels of oxidative stress-related factors in hippocampus tissue of the rats in various groups were detected by related kits； fluorescence probes of reactive oxygen species （ROS） were used to detect the levels of ROS in hippocampus tissue of the rats in various groups； TUNEL method was used to detect the TUNEL positive cell rates in hippocampus tissue of the rats in various groups. Western blotting method was used to detect the expression levels of mitochondrial fission， fusion and biogenesis-related proteins and nicotinamide adenine dinucleotide phoshate oxidase 4（Nox4） and nuclear factor E2-related factor 2（Nrf2） proteins； the expression levels of Nrf2 in hippocampus tissue of the rats in various groups were detected by immunofluorescence method. Results Compared with sham operation group， the neurological deficit score of the rats in model group was significantly increased （P<0.05）， the pathological damage of hippocampus tissue of the rats was obvious， the activities of superoxide dismutase（SOD） and glutathion peroxidase（GSH-Px） and the level of total antioxidant capacity（T-AOC） in hippocampus tissue were significantly decreased（P<0.05）， the levels of malonadehyde（MDA） and ROS and the TUNEL positive cell rate were significantly increased（P<0.05），the expression levels of dynamin-related protein 1 （DRP1）， fission protein 1（Fis1）， Nox4， and Nrf2 proteins were significantly increased （P<0.05），and the expression levels of optic atrophy 1（OPA1）， mitofusin 2（Mfn2）， peroxisome proliferator-activated receptor γ co-activator 1α（PGC-1α），and mitochondrial transcription factor A（TFAM） proteins were significantly decreased （P<0.05）. Compared with model group， the neurological deficit score of the rats in propofol postconditioning group was significantly decreased （P<0.05）， the pathological damage of hippocampus tissue of the rats was significantly improved， the levels of MDA and ROS and the TUNEL positive cell rate were signficantly increased（P<0.05）， the expression levels of DRP1， Fis1 and Nox4 proteins were significantly decreased （P<0.05）， and the expression levels of OPA1， Mfn2， PGC-1α， TFAM and Nrf2 proteins were significantly increased （P<0.05）. Conclusion Postconditioning of propofol can inhibit apoptosis and oxidative stress in hippocampus tissue of the rats with cerebral ischemia-reperfusion injury， promote mitochondrial fusion and biogenesis and inhibit mitochondrial fission， and improve the neurological damage of rats； its mechanism may be related to the regulation of Nox4/Nrf2 signaling pathway.

Key words: Propofol postconditioning, Cerebral ischemia-reperfusion injury, Oxidative stress, Mitochondrial damage, Nicotinamide adenine dinucleotide phosphate oxidase 4, Nuclear factor E2-related factor 2