米诺环素增加情绪有关脑区ΔFosB的表达来减轻LPS诱导的小鼠神经炎性反应  

Minocycline alleviates LPS-induced neuroinflammation by increasing the expression of ΔFosB in emotion-regulating brain regions in mice

作　　者：李岚岚 修建波 沈岩[1] 许琪[1] LI Lan-lan;XIU Jian-bo;SHEN Yan;XU Qi(State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China)

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院生物化学与分子生物学系医学分子生物学国家重点实验室

出　　处：《基础医学与临床》2019年第7期943-948,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81625008,31430048,31671115)

摘　　要：目的探究转录因子ΔFosB在米诺环素减轻脂多糖(LPS)诱导的神经炎性反应中的作用。方法成年C57BL/6小鼠连续3 d经腹膜内注射0.9%氯化钠溶液或米诺环素(50mg/kg),第3天再分别注射0.9%氯化钠溶液或LPS(0.83 mg/kg),注射后6或24 h取样。用免疫组化实验观察特定脑区小胶质细胞形态和ΔFosB的表达,以分析米诺环素对LPS导致神经炎性反应的抑制作用和ΔFosB的表达分布。用Image-Pro Premier 3D分析图像,用GraphPad Prism进行统计学分析。结果米诺环素可以有效减少蓝斑(LC)中LPS导致的小胶质细胞胞体面积的增加(P<0.05),减少中枢的炎性反应。同时,米诺环素增加了抑郁症相关脑区LC(P<0.001),臂旁核(LPB,P<0.05)和下丘脑室旁核(PVN,P<0.05)中ΔFosB的表达。结论米诺环素可能通过增加情绪有关脑区LC,LPB,PVN中ΔFosB的表达来减轻脂多糖诱导的神经炎性反应。Objective To investigate the role ofΔFosB as a transcription factor in the reduction of lipopolysaccharide(LPS)-induced neuroinflammation by minocycline.Methods Adult C57 BL/6 mice at 10 weeks of age received intraperitoneal(i.p.)injections of saline or minocycline(50 mg/kg)for three consecutive days.On the third day,mice were also injected via i.p.with saline or Escherichia coli LPS(0.83 mg/kg).The morphology of microglia indicating the state of neuroinflammation andΔFosB as a transcription factor was examined by immunohistochemistry.Images of the staining were analyzed with Image-Pro Premier 3 D.Statistical analysis was performed with GraphPad Prism.Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by the reduced activation of microglia in locus coeruleus(LC).Minocycline significantly increased the number ofΔFosB-positive neurons in LC,the lateral parabrachial nucleus(LPB)and paraventricular nucleus of the hypothalamus(PVN).Conclusions Minocycline alleviates LPS-induced neuroinflammation potentially by increasing the expression ofΔFosB in emotion-regulating brain regions including LC,LPB and PVN.

关 键 词：抑郁症 ΔFosB 米诺环素 小胶质细胞 

分 类 号：R319[医药卫生—基础医学]