Objective:To explore the mechanism of dexmedetomidine (DEX) regulating microglial (MG) polarization and neuroinflammation after traumatic brain injury (TBI) in rats.Methods:Forty-two adult male SD rats were randomly (random number) divided into the sham group, TBI group, TBI+DEX group (further divided into 1 d, 3 d and 7 d subgroups), TBI+NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC) group and TBI+DEX+PDTC group, with 6 animals in each group. The rat TBI model was established according to the modified Feeney free fall method. PDTC was intraperitoneally injected 1 h after modeling with a dose of 100 mg/kg, and DEX was intraperitoneally injected 2 h after modeling with a dose of 100 μg/kg. Modified neurological severity score (mNSS) was used to evaluate rat neurological function, ELISA was used to detect serum inflammatory factors, and rats’ damaged cortex was collected to detect the phenotype markers of MG and protein expressions of MyD88 and NF-κB p65, and immunofluorescence staining was used to observe the expression and nuclear entry of NF-κB p65 in MG in injured cortex. One-way and two-way ANOVA were used to compare the measurement data among multiple groups.Results:Compared with the sham group, the mNSS score was significantly higher in the TBI group, and DEX treatment significantly decreased the mNSS score of TBI rats ( P<0.05). ELISA and Western blot results showed that in the TBI group, the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in serum and M1 phenotype marker (TNF-α, IL-1β) in brain were increased, the expression of anti-inflammatory factor IL-10 in serum and M2 phenotype markers (arginase-1 and IL-10) in brain were decreased ( P<0.05), and DEX downregulated the expression of TNF-α, IL-1β in serum and M1 phenotype markers in brain, while upregulated the level of L-10 in serum and the M2 phenotype marker in brain ( P<0.05). In addition, the expression of MyD88 and the nuclear translocation of NF-κB p65 were inhibited in the DEX group, and this effect could be enhanced by PDTC. Conclusions:DEX modulates MG activation in TBI rats by inhibiting NF-κB nuclear translocation and reduces neuroinflammation.

目的 探讨早产儿脑损伤(脑室内出血和脑白质损伤)的危险因素.方法 2014年6月1日至2019年5月31日,在昆明医科大学第一附属医院分娩的出生胎龄28～33+6周的早产儿473例中,入住新生儿科的活产儿443例,排除顽固性低血糖、胆红素脑病、放弃治疗及死亡病例,共纳入392例.结合围产期病史及新生儿早期临床表现,以头颅磁共振成像诊断为主要依据,诊断脑室内出血及脑白质损伤.将患儿分为脑室内出血组(102例)、轻度脑白质损伤组(32例)、中重度脑白质损伤组(31例)及无脑损伤组(227例).统计学方法采用χ2检验、t检验和Logistic回归模型,分析早产儿不同类型脑损伤的危险因素.结果 392例胎龄28～33+6周的早产儿中,脑损伤发生率为42.1％(165/392),其中脑室内出血发生率为26.0％(102/392),脑白质损伤发生率为16.1％(63/392).Logistic回归模型显示,脑室内出血的危险因素:重度妊娠期高血压疾病(OR=2.287,95％CI:1.099～4.758,P<0.05)、支气管肺发育不良(OR=2.670,95％CI:1.418～5.029,P<0.01)、晚发型败血症(OR=2.318,95％CI:1.234～4.357,P<0.01)、机械通气(OR=1.936,95％CI:1.067～3.517,P<0.05).轻度脑白质损伤的危险因素:临床型绒毛膜羊膜炎(OR=9.864,95％CI:2.364～41.155,P<0.05)、新生儿窒息(OR=3.319,95％CI:1.394～7.906,P<0.05)、脐动脉血气pH<7.00(OR=4.953,95％CI:1.527～13.024,P<0.05).中重度脑白质损伤的危险因素:重度妊娠期高血压疾病(OR=4.213,95％CI:1.473～12.052,P<0.05)、机械通气(OR=5.029,95％CI:1.914～13.193,P<0.05).结论 早产儿不同类型的脑损伤存在不同的危险因素.重度妊娠期高血压疾病及机械通气为脑室内出血及中重度脑白质损伤的共同高危因素,应引起高度重视.

神经调节素1(Nrg-1)是神经调节蛋白家族的生长因子,在神经系统的发育和修复中起重要作用.Nrg-1通过蛋白酪氨酸激酶受体表皮生长因子ErbB1/2/3/4受体家族和多种细胞内途径传递信号.遗传学和药理学研究已经确认Nrg-1及其ErbB受体在神经系统发育和修复中的关键作用,包括神经元迁移、神经元分化、髓鞘重建以及突触和神经-肌肉接头的发育.文中就Nrg-1/ErbB信号通路在脊髓损伤修复过程中的作用机制进行综述.

铁自噬(ferritinophagy)是一种调节细胞内铁代谢的选择性自噬,由核受体共激活因子4(NCOA4)介导细胞内铁蛋白转运到自噬溶酶体中降解释放出游离铁,用于多种铁依赖的生理过程.正常生理情况下铁自噬维持着细胞内铁元素的平衡.当铁自噬过度激活时,细胞内过量的铁沉积诱导谷胱甘肽(GS H)耗竭以及谷胱甘肽过氧化物酶4(GPX4)的表达减少,导致细胞膜结构崩溃和破裂,最终引起细胞的铁死亡(ferroptosis).已有研究表明,氧化应激、炎症、兴奋性毒素和凋亡在中枢神经系统损伤的病理生理过程中起着重要作用.近年来,对铁死亡这一以铁依赖性脂质过氧化积累为特征的调节性细胞死亡与中枢神经系统疾病的关系研究越来越多.本文就铁自噬与铁死亡在中枢神经系统疾病中的作用研究进展进行综述.