| Objective: To explore the role of Janus Kinase2/signal transducer and activator of transcription3(JAK2/STAT3) signaling pathway in the reduction of hippocampal injury by propofol in rats after autogenous orthotropic liver transplantation.Methods: Thirty-two healthy male SpragueDawley rats, 8~10 weeks old, weighting 220~250g, were randomly divided into four groups using a random number table(n=8 each): sham operation group(group S),autogenous orthotropic liver transplantation group(group I); autogenous orthotropic liver transplantation + propofol postconditioning group(group P); autogenous orthotropic liver transplantation +AG490 group(group A). Rats in the group S only underwent simple laparotomy and were freed the corresponding blood vessels. The model of autogenous orthotropic liver transplantation was established in group I. In group P, propofol(20 mg · kg-1 · h-1) was infused for 30 min through right femoral vein immediately after reperfusion. In group A, AG490(5 mg/kg) was injected intraperitoneal for 30 min before incision and the other operations were same with group I. Rats were sacrificed at 6h after reperfusion, whose blood sample and hippocampus were harvested for determination. The serum levels of TNF-alpha?IL-6?S100? and NSE were tested by ELISA kits. The levels of MDA,SOD and NO in hippocampus were also detected. The expression of JAK2,STAT3 and iNOS mRNA was analyzed by real-time PCR. The protein expression levels of p-JAK2 and p-STAT3 were detected by Western blot. The pathological changes of rat hippocampal tissue and cell apoptosis were observed under the light microscope. The results were analyzed using SPSS21.0 statistical software, and there was a statistically significant difference when P<0.05.Results: Compared with group S,the serum levels of S100? and NSE were significantly increased in the other groups. The activity of MDA and NO were significantly increased, and the activity of SOD was decreased in the hippocampus. The expression of JAK2,STAT3 and iNOS mRNA were up-regulated and the apoptotic index increased in other groups. Compared with group S,the serum levels of S100?and NSE were increased in other groups. The activity of MDA and NO were increased, and the activity of SOD was decreased in the hippocampus. The expression of JAK2,STAT3, iNOS mRNA, p-JAK2, p-STAT3 were up-regulated and the apoptotic index increased in other groups. Meanwhile, the pathological injury of hippocampal tissue were increased. Compared with group I,the serum levels of S100? and NSE were decreased in group P and group A. The activity of MDA and NO were decreased, and the activity of SOD was increased in the hippocampus. The expression of JAK2,STAT3 and iNOS mRNA and p-JAK2, p-STAT3 protein were down-regulated and the apoptotic index decreased in group P and group A. Compared with group P,the serum levels of S100 and NSE, the activity of MDA and NO were decreased, and the activity of SOD, the expression of JAK2,STAT3,and iNOS mRNA were down-regulated and the apoptotic index no significant difference. Under light microscope, the structure of rat hippocampus in group S was intact, and the cells arranged in uniform. The hippocampus of rats in group I were edema, cell disorder, hippocampal pyramidal cell nuclear pyknosis and degeneration. The pathological changes of hippocampus in group P were significantly less than that of group I, and the pathological changes of A group were similar to group P.Conclusion:1?OLAT causes rats hippocampus ischemia reperfusion injury, which was related to the inflammatory reaction, oxidative stress and cell apoptosis.2?Propofol can reduce the hippocampus injury caused by autogenous orthotropic liver transplantation in rats, and the mechanism was related to inhibition of JAK/STAT siganling pathway. |
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