Effect of propofol on JAK2/STAT3 signaling pathway in hippocampus of rats undergoing orthotopic liver transplantation

Objective To evaluate the effect of propofol on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the hippocampus of rats undergoing orthotopic liver transplantation. Methods Twenty-four healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-250 g, were randomly divided into 3 groups (n=8 each) using a random number table: sham operation group (group S); orthotopic liver transplantation group (group O); propofol group(group P). After the rats were anesthetized with chloral hydrate, the model of orthotopic liver transplantation was established according to the method described by Nozato et al. in O and P groups.In group P, 30 min infusion of propofol was started at a rate of 20 mg·kg-1·h-1 via the right femoral vein immediately after onset of reperfusion.At 6 h of reperfusion, blood samples were collected from the infrahepatic vena cava, and then the rats were sacrificed.The hippocampi were harvested for determination of malondialdehyde (MDA) and nitric oxide (NO) contents and superoxide dismutase (SOD) activity.The serum levels of S100β protein and neuron-specific enolase (NSE) were determined by enzyme-linked immunosorbent assay.The expression of JAK2, STAT3 and inducible nitric oxide synthase (iNOS) mRNA was detected by quantitative real-time polymerase chain reaction.The pathological changes of hippocampal tissues were examined under the light microscope, and the cell apoptosis was measured using TUNEL.The apoptotic index was calculated. Results Compared with group S, the serum levels of S100β protein and NSE were significantly increased, the contents of MDA and NO were significantly increased, the activity of SOD was significantly decreased, the expression of JAK2, STAT3 and iNOS mRNA was significantly up-regulated, the apoptotic index was significantly increased (P<0.05), and the pathological changes of hippocampal tissues were significantly aggravated in the other groups.Compared with group O, the serum levels of S100β protein and NSE were significantly decreased, the contents of MDA and NO were significantly decreased, the activity of SOD was significantly increased, the expression of JAK2, STAT3 and iNOS mRNA was significantly down-regulated, the apoptotic index was significantly decreased (P<0.05), and the pathological changes of hippocampal tissues were significantly reduced in P group. Conclusion Propofol reduces injury to the hippocampus through blocking JAK2/STAT3 signaling pathway in the rats undergoing orthotopic liver transplantation. Key words: Janus kinase 2; STAT3 transcription factor; Signal transduction; Propofol; Liver transplantation; Reperfusion injury; Hippocampus