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 leptin group(L group), with 18 rats in each group.Orthotopic liver transplantation was performed to establish 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 examination of the pathological changes in hippocampal CA1 region(with a light microscope) and for determination 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 prolonged, 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 expression 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. Key words: Leptin; Liver transplantation; Reperfusion injury; Cognition disorders
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