OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts n...OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts neuroprotection after cerebral ischemia.However,whether OEA affects the outcomes of diabetes-induced encephalopathy(DE) requires further study.METHODS The chronic effects of OEA on DE were evaluated in C57BL/6 and PPARαknockout mice,individually.The cognitive function was assessed with Morris water maze.The expression of receptor for advanced glycation end products(RAGE) and phosphorylation of Tau in mice hippocampus were determined using Western blotting.The influence of OEA in neuron loss and neuroplasticity were assessed with immunofluorescent staining and Western blotting.RESULTS OEA markedly ameliorated performance in the Morris water maze,which was correlated with its capabilities of suppressing glycometabolism and phosphorylation of Tau in the hippocampus.OEA offered protection from diabetes-induced impairments in hippocampal neuroplasticity.Furthermore,the changes in Morris water maze performance and neuron loss could not be observed in PPARα knockout mouse models with OEA administration.CONCLUSION The ability of OEA to control PPARα signaling can serve as a novel neuroprotective approach for the treatment of diabetes-induced encephalopathy.展开更多
目的:探讨过氧化物酶体增殖物激活受体α(PPARα)介导CCAAT/增强子结合蛋白同源蛋白(CHOP)信号分子在急性肝衰竭小鼠炎症反应中的作用机制。方法:以C57BL/6小鼠为研究对象,腹腔注射D-氨基半乳糖(D-GalN)联合脂多糖(LPS)建立小鼠急性肝...目的:探讨过氧化物酶体增殖物激活受体α(PPARα)介导CCAAT/增强子结合蛋白同源蛋白(CHOP)信号分子在急性肝衰竭小鼠炎症反应中的作用机制。方法:以C57BL/6小鼠为研究对象,腹腔注射D-氨基半乳糖(D-GalN)联合脂多糖(LPS)建立小鼠急性肝衰竭模型。用Wy-14643激活PPARα、用质粒促进CHOP表达,检测小鼠肝脏病理改变、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酯(AST)评价肝脏功能,实时荧光定量PCR检测肝组织中炎性因子mRNA表达水平。LPS刺激巨噬细胞建立炎症模型,用siRNA抑制PPARα、CHOP的表达,实时荧光定量PCR检测细胞中炎性因子mRNA表达水平。结果:D-GalN/LPS诱导急性肝衰竭小鼠中,促进PPARα活性抑制了小鼠肝脏出血和炎症,降低了血清转氨酶水平,也降低了肝组织中炎症因子的mRNA水平( P < 0.01)。促进CHOP表达,逆转了PPARα激活带来的肝脏保护作用,肝脏损伤加重,炎症因子表达增加( P < 0.01)。细胞水平上,PPARα活性抑制促进了炎症因子的增高( P < 0.01),同时抑制CHOP活性后使炎症因子重新下降( P < 0.01)。 结论:急性肝衰竭肝损伤中PPARα和CHOP分子是调节炎症反应的重要信号分子,促进PPARα可下调CHOP抑制炎症因子发挥对小鼠肝衰竭的保护性作用。展开更多
基金Fun-damental Research Funds for the Central Universities (20720180042)Health Science ResearchPersonnel Training Program of Fujian Province(2018-CXB-30)+2 种基金Natural Science Foundation of Fujian, China (2016J014152016D024)Science and Technology Project of Xi
文摘OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts neuroprotection after cerebral ischemia.However,whether OEA affects the outcomes of diabetes-induced encephalopathy(DE) requires further study.METHODS The chronic effects of OEA on DE were evaluated in C57BL/6 and PPARαknockout mice,individually.The cognitive function was assessed with Morris water maze.The expression of receptor for advanced glycation end products(RAGE) and phosphorylation of Tau in mice hippocampus were determined using Western blotting.The influence of OEA in neuron loss and neuroplasticity were assessed with immunofluorescent staining and Western blotting.RESULTS OEA markedly ameliorated performance in the Morris water maze,which was correlated with its capabilities of suppressing glycometabolism and phosphorylation of Tau in the hippocampus.OEA offered protection from diabetes-induced impairments in hippocampal neuroplasticity.Furthermore,the changes in Morris water maze performance and neuron loss could not be observed in PPARα knockout mouse models with OEA administration.CONCLUSION The ability of OEA to control PPARα signaling can serve as a novel neuroprotective approach for the treatment of diabetes-induced encephalopathy.
文摘目的:探讨过氧化物酶体增殖物激活受体α(PPARα)介导CCAAT/增强子结合蛋白同源蛋白(CHOP)信号分子在急性肝衰竭小鼠炎症反应中的作用机制。方法:以C57BL/6小鼠为研究对象,腹腔注射D-氨基半乳糖(D-GalN)联合脂多糖(LPS)建立小鼠急性肝衰竭模型。用Wy-14643激活PPARα、用质粒促进CHOP表达,检测小鼠肝脏病理改变、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酯(AST)评价肝脏功能,实时荧光定量PCR检测肝组织中炎性因子mRNA表达水平。LPS刺激巨噬细胞建立炎症模型,用siRNA抑制PPARα、CHOP的表达,实时荧光定量PCR检测细胞中炎性因子mRNA表达水平。结果:D-GalN/LPS诱导急性肝衰竭小鼠中,促进PPARα活性抑制了小鼠肝脏出血和炎症,降低了血清转氨酶水平,也降低了肝组织中炎症因子的mRNA水平( P < 0.01)。促进CHOP表达,逆转了PPARα激活带来的肝脏保护作用,肝脏损伤加重,炎症因子表达增加( P < 0.01)。细胞水平上,PPARα活性抑制促进了炎症因子的增高( P < 0.01),同时抑制CHOP活性后使炎症因子重新下降( P < 0.01)。 结论:急性肝衰竭肝损伤中PPARα和CHOP分子是调节炎症反应的重要信号分子,促进PPARα可下调CHOP抑制炎症因子发挥对小鼠肝衰竭的保护性作用。
