Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in sever...Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in several animal models of central nervous system disease.However,few reports have examined whether FTY720 could mitigate postoperative cognitive dysfunction.In this study,we investigated whether FTY720 could prevent postoperative neurocognitive impairment in mice subjected to D-galactose-induced aging.We induced an accelerated model of aging by administering an intraperitoneal injection of D-galactose.Subsequently,we performed a partial hepatolobectomy under sevoflurane anesthesia.FTY720(1 mg/kg)was administered intraperitoneally 3 hours before and 24 hours after anesthesia and surgery.Our results indicated that anesthesia and surgery significantly impaired spatial memory in the Y-maze test 6 hours after surgery.We also found that problem solving ability and long-term memory in the puzzle box test on postoperative days 2–4 were significantly improved by FTY720 treatment.Immunohistochemical staining and western blot assay demonstrated that FTY720 significantly inhibited microglial activation in the hippocampal CA1 region of mice 6 hours and 3 days after anesthesia,and down-regulated the expression of synaptic-related proteins postsynaptic density protein 95 and GluR2 in the hippocampus.These results indicate that FTY720 improved postoperative neurocognitive dysfunction in mice subjected to D-galactose-induced aging.This study was approved by the Experimental Animal Ethics Committee of the Third Xiangya Hospital of Central South University of China(approval No.LLSC(LA)2016-025)on September 27,2016.展开更多
基金supported by the National Natural Science Foundation of China,No.81500932(YW)
文摘Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in several animal models of central nervous system disease.However,few reports have examined whether FTY720 could mitigate postoperative cognitive dysfunction.In this study,we investigated whether FTY720 could prevent postoperative neurocognitive impairment in mice subjected to D-galactose-induced aging.We induced an accelerated model of aging by administering an intraperitoneal injection of D-galactose.Subsequently,we performed a partial hepatolobectomy under sevoflurane anesthesia.FTY720(1 mg/kg)was administered intraperitoneally 3 hours before and 24 hours after anesthesia and surgery.Our results indicated that anesthesia and surgery significantly impaired spatial memory in the Y-maze test 6 hours after surgery.We also found that problem solving ability and long-term memory in the puzzle box test on postoperative days 2–4 were significantly improved by FTY720 treatment.Immunohistochemical staining and western blot assay demonstrated that FTY720 significantly inhibited microglial activation in the hippocampal CA1 region of mice 6 hours and 3 days after anesthesia,and down-regulated the expression of synaptic-related proteins postsynaptic density protein 95 and GluR2 in the hippocampus.These results indicate that FTY720 improved postoperative neurocognitive dysfunction in mice subjected to D-galactose-induced aging.This study was approved by the Experimental Animal Ethics Committee of the Third Xiangya Hospital of Central South University of China(approval No.LLSC(LA)2016-025)on September 27,2016.
文摘目的探讨芬戈莫德(fingolimod,FTY720)对试验性自身免疫性脑脊髓炎(EAE)小鼠脑组织中一氧化氮(NO)含量和诱导型一氧化氮合酶(i NOS)表达的影响。方法 48只雌性C57BL/6小鼠随机平均分为3组,EAE组运用MOG35-55构建EAE小鼠模型;CFA组由生理盐水代替MOG35-55构建模型;FTY720干预组在EAE基础上给予FTY720腹腔注射,CFA组、EAE组给予生理盐水腹腔注射。HE染色和LBF染色观察炎症情况和脱髓鞘情况,ELLISA检测小鼠脑组织中的NO含量,RT-PCR检测的诱导型一氧化氮合酶(i NOS)mRNA表达。结果 FTY720组EAE小鼠较EAE组临床症状减轻,炎症程度和脱髓鞘程度减轻(P<0.05)。FTY720组小鼠脑组织NO含量较EAE组降低(P<0.05),i NOS mRNA表达量降低(P<0.05)。结论 FTY720能抑制EAE小鼠脑组织中i NOS mRNA表达,从而减少NO含量。
