首页|下丘脑/延髓轴调节创伤性颅脑损伤后外周脂质代谢

下丘脑/延髓轴调节创伤性颅脑损伤后外周脂质代谢

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目的 探究创伤性颅脑损伤(TBI)后下丘脑相关交感兴奋与外周脂质代谢改变相关性,为TBI重症营养管理提供依据.方法 将8周龄C57BL/6小鼠随机分为Sham组、TBI-1 d组、TBI-3 d组、TBI-7 d组,每组6只,TBI组进行重物撞击模型,Sham组进行头皮切开缝合处理;于对应时间点处死并留取相应标本.通过油红染色或免疫荧光染色明确各组中棕色脂肪及肝脏脂滴情况;通过Western blot检测肝脏脂噬相关蛋白变化;通过c-Fos免疫荧光染色检测TBI后下丘脑区、中缝核区、延髓头端腹外侧区神经元激活情况;通过分析单细胞数据明确下丘脑区能量代谢相关神经元在TBI后分子水平的变化.结果 (1)TBI后棕色脂肪脂滴大小明显减小,相同视野下TBI组棕色脂肪细胞数量增加.(2)肝脏脂滴包被蛋白-2(PLIN2)荧光染色显示阳性颗粒在TBI后增加,提示肝脏脂质蓄积增多;Western blot结果示TBI后肝脏脂噬相关蛋白增加,提示肝脏脂质利用能力增强.(3)下丘脑区、中缝核区、延髓头端腹外侧区c-Fos荧光染色结果提示TBI后激活神经元增多.(4)单细胞结果提示TBI后下丘脑区神经元激素调节、能量代谢、兴奋性神经元活动等信号出现明显变化.结论 TBI后下丘脑/延髓区神经元激活可能与交感神经高反应性有关,进而促进棕色脂肪及肝脏脂质代谢.
Hypothalamus/medulla oblongata axis regulates peripheral lipid metabolism after traumatic brain injuries
Objective To explore the correlation between hypothalamic sympathetic hyperresponsiveness and peripheral lipid metabolism change after traumatic brain injuries(TBI),and to shed light on nutritional manage-ment for severe TBI.Methods Eight-week C57BL/6 mice were randomly divided into Sham group,TBI-1 d group,TBI-3 d group,and TBI-7 d group,with 6 mice in each group.Mice in the TBI groups experienced a heavy object strike,while those in the Sham group only underwent scalp incision and suture.Mice were executed and sampled at the corresponding time points.The lipid droplets of the liver and the brown adipose tissue were identified by oil-red staining and immunofluorescence staining;the change of liver lipophagy in different groups was detected through Western blot;the activation of neurons in the hypothalamus,raphe nuclei and rostral ventrolateral medulla was de-tected by c-Fos immunofluorescence staining;and the molecular level changes in energy metabolism-related neurons in the hypothalamic region after TBI were identified by analyzing single-cell data.Results(1)The size of lipid droplets in brown adipose tissue decreased significantly after TBI,and the cell density of brown adipose tissue in-creased in TBI groups,compared with the Sham group.(2)Oil red staining showed a slight increase in liver lipid droplets after TBI;meanwhile,fluorescence staining indicated an increase in perilipin-2(PLIN2)positive particles after TBI.An elevation in liver lipophagy-related proteins after TBI was detected through Western blot,indicating a boost in liver lipid utilization ability.(3)The c-Fos fluorescence staining in the hypothalamus,raphe nuclei and rostral ventrolateral medulla oblongata revealed that the number of activated neurons increased after TBI.(4)Sin-gle-cell results showed significant signal changes in hormone regulation,energy metabolism,and excitatory neuronal activity in the hypothalamic neurons after TBI.Conclusion Activation of neurons in the hypothalamus/medulla af-ter TBI may be related to sympathetic hyperresponsiveness,thus promoting the lipid metabolism of brown adipose tis-sue and liver.

Traumatic brain injuriesLipid metabolismHypothalamusSympathetic hyperresponsiveness

费茂星、李振兴、罗诗樵、周梦良、王汉东

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南京大学医学院附属金陵医院神经外科,南京 210008

南京医科大学,南京 211166

南京医科大学附属明基医院神经外科,南京 210019

创伤性颅脑损伤 脂质代谢 下丘脑 交感神经高反应性

国家自然科学基金面上项目国家自然科学基金青年基金国家自然科学基金青年基金

8227142682101461

2024

创伤外科杂志
第三军医大学,大坪医院,野战外科研究所

创伤外科杂志

CSTPCD
影响因子:1.017
ISSN:1009-4237
年,卷(期):2024.26(3)
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