目的:探讨褪黑素（MT）对脂多糖（LPS）诱导的脓毒症幼鼠胼胝体内少突胶质细胞分化成熟的影响。方法:新生P1d SD幼鼠随机（随机数字法）分为对照组、脓毒症模型组和褪黑素治疗组。动物以1 mg/kg剂量腹腔注射LPS诱导脓毒症模型，褪黑素治疗组先以1 mg/kg剂量腹腔注射LPS，0.5 h后以10 mg/kg剂量腹腔注射褪黑素,1次/d,连续7 d。Western blot和免疫荧光检测上述三组6 h、1 d、3 d后胼胝体内IL-6蛋白的表达，7、14、28 d后胼胝体内Olig1、Olig2以及MAG蛋白的表达。细胞实验采用BV-2小胶质细胞株，分别用LPS、褪黑素以及褪黑素受体抑制剂luzindole干预细胞，免疫荧光和Western blot检测干预后BV-2细胞IL-6蛋白的表达，并收集各组BV-2细胞条件培养基干预分离纯化后的原代OPC细胞。Western blot检测干预后OPC细胞Olig1、Olig2以及MAG蛋白的表达。采用SPSS 20.0统计软件分析，数据分别采用双因素及单因素方差分析，以n P<0.05为差异有统计学意义。n 结果:与脓毒症模型组相比，褪黑素可明显降低腹腔注射LPS 6 h、1 d、3 d后胼胝体内IL-6表达（n P<0.05），可增加7、14、28 d后胼胝体内Olig1、Olig2以及MAG的表达（n P<0.05）。褪黑素可降低LPS刺激下BV-2细胞IL-6的高表达（n P<0.05），此作用可被褪黑素受体抑制剂阻断（n P<0.05）。LPS+褪黑素的BV2细胞条件培养基可逆转LPS的BV2细胞条件培养基引起的原代OPC细胞中Olig1、Olig2及MAG蛋白低表达（n P<0.05）。n 结论:褪黑素可通过其受体抑制脓毒症幼鼠胼胝体内炎症反应，促进脓毒症幼鼠胼胝体内少突胶质细胞分化成熟，提示褪黑素可以改善脓毒症幼鼠脑室周边白质内神经炎症反应及轴突低髓鞘化。“,”Objective:To investigate the effect of melatonin on oligodendrocyte maturation and differentiation in corpus callosum of septic neonatal rats induced by systemic lipopolysaccharide (LPS) injection.Methods:Sprague-Dawley rats were randomly allocated into the control group, septic experimental group, and melatonin group. In the septic experimental group, rats were intraperitoneally administrated with lipopolysaccharide (LPS) (1 mg/kg). In the melatonin group, melatonin was intraperitoneally administered (10 mg/kg) at 0.5 h after LPS injection. The expression level of IL-6, olig1, olig2, and the MAG protein were detected by Western blot at different time points in the three groups. BV-2 cells were used in vitro. For drug administration, the effect of LPS, melatonin and melatonin receptor antagonist, luzindole, on IL-6 expression in BV-2 microglia cell was determined by Western blot. The medium of BV2 cell were collected to treat primary OPCs. The expression level of olig1, olig2 and MAG protein in primary OPCs were detected by Western blot. SPSS 20.0 statistical software was used for analysis, and the data were analyzed by one-way ANOVA and two-way ANOVA. Differences were considered to be statistically significantly if n P<0.05.n Result:Compared with the LPS group, the expression of IL-6 was significantly decreased in the corpus callosum at 6 h, l d, and 3 d in the melatonin group (n P<0.05). The expression of olig1, olig2 and MAG protein were increased at day 7, 14, and 28 in the melatonin group compared with the LPS group (n P<0.05). In vitro the expressions of IL-6 was significantly increased after LPS treatment (n P<0.05), but was decreased in the LPS+melatonin treatment group (n P<0.05). After treatment with melatonin receptor inhibitor, luzindole, the expressions level of IL-6 was increased (n P<0.05). The expression of olig1, olig2 and MAG protein were decreased with conditioned medium in the LPS BV2 cell group than the control group in the primary OPCs (n P<0.05). However, those were increased with conditioned medium in the LPS+melatonin BV2 cell group than the LPS group (n P<0.05).n Conclusions:Melatonin may inhibit the inflammation response in the corpus callosum through its receptor, and may promote the maturation and differentiation of oligodendrocyte, suggesting that melatonin may have therapeutic effect on neuroinflammation and axonal hypomyelination on PWM in septic neonatal rats.