Effects of leptin on brain injury and long-term cognitive function in rats undergoing orthotopic liver transplantation / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of leptin on brain injury and long-term cognitive function in rats undergoing orthotopic liver transplantation. Methods Ninety clean-grade male Sprague-Dawley rats, aged 3 months, weighing 200-250 g, were divided into 3 groups by a random number table method: sham operation group ( S group) , liver ischemia-reperfusion ( I∕R) group ( I∕R group) and lep-tin group ( L group) , with 18 rats in each group. Orthotopic liver transplantation was performed to estab-lish the model of liver I∕R injury in I∕R and L groups. Leptin 1 mg∕kg was intraperitoneally injected at the onset of ischemia in L group, and the equal volume of normal saline was given instead of leptin in S and I∕R groups. Twelve rats in each group were sacrificed at 3 days after operation, and brains were removed for ex-amination of the pathological changes in hippocampal CA1 region ( with a light microscope) and for determi-nation of apoptosis in hippocampal neurons ( by TUNEL assay) and expression of aquaporin 4 ( AQP4) and protein kinase C ( PKC) in the hippocampus ( by Western blot) . The apoptosis rate was calculated. The remaining 6 rats in each group underwent a Morris water maze test at 30 days after surgery to evaluate long-term cognitive function. Results Compared with S group, the apoptosis rate of hippocampal neurons was significantly increased, the expression of AQP4 and PKC was up-regulated, the escape latency was pro-longed, and the time of staying at the platform quadrant was shortened in I∕R and L groups (P<0. 05). Compared with I∕R group, the apoptosis rate of hippocampal neurons was significantly decreased, the ex-pression of AQP4 and PKC was down-regulated, the escape latency was shortened, and the time of staying at the platform quadrant was prolonged in L group (P<0. 05). Conclusion Leptin can reduce the brain damage in rats undergoing orthotopic liver transplantation, the mechanism may be related to down-regulating the expression of PKC and AQP4, and leptin can also improve long-term cognitive function after orthotopic liver transplantation in rats.