Effect of leptin on pyroptosis in hippocampal cells during brain injury in a rat model of orthotopic liver transplantation / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of leptin on pyroptosis in hippocampal cells during brain injury in a rat model of orthotopic liver transplantation (OLT).Methods:Fifty-four clean-grade male Sprague-Dawley rats, aged 12 weeks, weighing 200-250 g, were divided into 3 groups( n=18 each)by a random number table method: sham operation group (S group), OLT-induced brain injury group (Liver group) and leptin group (Lep group). The model of OLT was established according to the " two-cuff" technique in anesthetized rats in Liver and Lep groups.The perihepatic ligament was only isolated and freed in S group.Leptin 1 mg/kg was intraperitoneally injected immediately after portal vein occlusion in Lep group.The equal volume of normal saline was intraperitoneally injected at the same time point in S group and Liver group.Twelve rats in each group were selected on day 3 after surgery and sacrificed, and the hippocampal tissues were obtained for examination of the pathological changes (with a light microscope) and for determination of the expression of NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-1beta (IL-1β), IL-18 and gasdermin D (GSDMD) mRNA (by real-time polymerase chain reaction) and expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD (by Western blot). Morris water maze test was performed in the remaining 6 rats in each group on day 30 after surgery. Results:Compared with S group, the count of viable neurons in hippocampi was significantly decreased, the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was up-regulated, the time of staying at the platform quadrant was shortened, and the escape latency was prolonged in Liver and Lep groups ( P<0.05). Compared with Liver group, the count of viable neurons in hippocampi was significantly increased, the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was down-regulated, the time of staying at the platform quadrant was prolonged, and the escape latency was shortened in Lep group ( P<0.05). The pathological changes of hippocampal tissues were significantly attenuated in Liver group when compared with Lep group. Conclusion:The mechanism by which leptin reduces brain injury is related to inhibiting pyroptosis in hippocampal cells in a rat model of OLT.