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高压氧治疗对病毒性脑炎患儿脑神经功能、Th17/Treg细胞水平以及TLR2/NF-κB通路的影响

Effects of hyperbaric oxygen therapy on neurological function, Th17/Treg levels and TLR2/NF-κB pathway in children with viral encephalitis

摘要目的:探究高压氧治疗(hyperbaric oxygen therapy,HBOT)对病毒性脑炎患儿神经功能、血清辅助性T细胞17(Th17)/调节性T细胞(regulatory T cells,Treg)水平以及Toll样受体2(Toll-like receptor 2,TLR2)/核因子κB(nuclear factor-kappa-B,NF-κB)通路的影响。方法:选择重庆市大渡口区人民医院儿科2017年4月至2019年4月收治的病毒性脑炎患儿76例作为研究对象,按随机数字表法分为对照组和HBOT组(每组38例)。对照组患儿接受常规治疗,HBOT组在对照组基础上联合HBOT。对比2组的临床治疗效果、脑电图(EEG)检查结果、简易智力状态检查量表(mini-mental state examination, MMSE)、血清炎性因子、中枢神经特异性蛋白(central nerve specific protein,S100β)、神经元特异性烯醇化酶(neuron specific enolase,NSE)、外周血Th17/Treg以及TLR2/NF-κB通路水平。治疗前2组各项指标比较差异均无统计学意义( P>0.05)。 结果:HBOT组临床症状持续时间均显著短于对照组( P<0.05),HBOT组癫痫发作次数显著少于对照组( P<0.05)。治疗后HBOT组中度和重度EEG异常的比例显著少于对照组( P<0.05),EEG恢复正常的比例显著高于对照组( P<0.05),HBOT组EEG恢复时间显著短于对照组( P<0.05)。治疗后HBOT组的MMSE评分(28.16±8.29)高于对照组(20.21±4.40)( P<0.05)。HBOT组的白细胞介素1(IL-1)、C反应蛋白(CRP)、S100β和NSE水平显著低于对照组( P<0.05)。HBOT组的Th17[(0.024±0.004)%]显著低于对照组[(0.028±0.001)%]( P<0.05),Treg[(0.016±0.003)%]显著高于对照组[(0.014±0.004)%]( P<0.05)。HBOT组的TLR2、Myd88和NF-κB蛋白水平均显著低于对照组( P<0.05)。HBOT组未发现HBOT相关不良反应。 结论:HBOT可提高对病毒性脑炎患儿的疗效,减少癫痫的发生,并发挥脑保护作用,这可能与HBOT具有抑制TLR2/NF-κB通路、调节Th17/ Treg平衡的作用有关。

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abstractsObjective:To investigate the effects of hyperbaric oxygen therapy (HBOT) on neurological function, Th17/Treg levels, and TLR2/NF-κB pathway in children with viral encephalitis (VE).Methods:A total of 76 children with VE admitted to the Dadukou People’s Hospital between April 2017 and April 2019 were selected as the research subjects and randomly assigned to two groups ( n=38) by the random number table method. The children in the control group received conventional treatment, and those in the HBOT group additionally received HBOT. The clinical treatment effects, the results of electroencephalogram (EEG) examination, the mini-mental state examination(MMSE), the serum inflammatory factors, the central nerve specific protein (S100β), the neuron-specific enolase (NSE), the peripheral blood Th17/ regulatory T cells (Treg), and TLR2/NF-κB pathway levels were compared. There were no significant differences in those indicators between the two groups before treatment ( P>0.05). Results:The time period for the clinical symptoms to disappear in the HBOT group was significantly shorter than that in the control group ( P<0.05). The times of seizure onset in the HBOT group were significantly less than those in the control group ( P<0.05). After treatment, the proportions of moderate and severe EEG abnormalities in the HBOT group were significantly lower than those in the control group ( P<0.05), the proportion of EEG returning to normal state was significantly higher than that in the control group ( P<0.05), and the recovery time period of EEG in the HBOT group was significantly shorter than that in the control group ( P<0.05). After treatment, the MMSE score of the HBOT group was higher than that of the control group [(28.16±8.29)>(20.21±4.40), P<0.05]. The levels of IL-1, CRP, S100β, and NSE in the HBOT group were significantly lower than those in the control group ( P<0.05). After treatment, the level of Th17 in the HBOT group was significantly lower than that in the control group [(0.024±0.004)% vs. (0.028±0.01)%, P<0.05], and the level of Treg was significantly higher than that in the control group [(0.016±0.003)% vs. (0.014±0.004)%, P<0.05]. The levels of TLR2, Myd88, and NF-κB protein in the HBOT group were significantly lower than those in the control group ( P<0.05). No HBOT-related adverse reaction was found in the HBOT group. Conclusion:The treatment combined with HBOT can improve the curative effect in the children with VE, reduce the times of seizure onset, and protect brain. This may be related to the role of HBOT in inhibiting TLR2/NF-κB pathway and regulating the balance of Th17/Treg.

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